Science topic

Neuroprotection - Science topic

“Neuroprotection” is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, and spinal cord injury. Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons.
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I want to study the neuroprotection of ghrelin in mice neurological disease model, but there is differences in this drug between human and rat, which one i should choose since both type of drug has been used in the published paper. Thanks.
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Both
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Magnesium Sulphate is administered to pregnant women during preterm labour for fetal neuroprotection. Would like to know about any studies which have been done to evaluate its beneficial effects during early neonatal period.
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Interesting topic
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MgSO4 is usually administered during preterm labour for neuroprotection. I would like to know whether there are any beneficial effects during early neonatal period also.
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Really interesting topic
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I have been working on a TBI mouse model and looking at AQP4. The literature provided by abcam shows the western blot data to have a band at 46 kDa and another one at 20kDa that they cannot identify. My blots have a double band at 48 and 46 kDa and a large band at 20 kDa. Does anyone have any experience working with this antibody? Any suggestions or ideas about what these bands represent?
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I have been looking into this, as well. I have seen bands at ~90kDa, at ~50kDa, and at ~20kDa. Primary literature points to the ~90kDa band as likely some SDS-insoluble oligomer. But, I can't seem to find anything for the 20kDa band. Have you found anything yet?
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I am working on estradiol neuroprotection impact and measuring its concentration in hippocampal female rats in their diestrus phase by 17beta-Estradiol ELISA (Diagnostics Biochem Canada). To extract estradiol from hippocampus the tissue was homogenized in 150µl PBS and centrifuged at 15,000g for 30 min at 4ºC and supernatants were collected. The problem is almost no level of estradiol was detected through this method.
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I will try to explain it better. The average concentration of estradiol in brain is of little value. Then, even having an excellent method of extraction of estradiol from brain tissue the data will tell you little. Unless yo are measuring pharmacokinetics/biodistribution after estradiol administration.
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We would like to roughtly assess the potential neuroprotective ability of a certain agent to prevent people from developing Parkinson's disease (PD). PD has an incidence of 1% in the general population over 60 years. We are planning to conduct a retrospective study on a group of people, who have all been exposed to this agent for many years. The potential beneficial effect of the agent would also consider information about time of exposure to the agent and the estimated total received dosage of the agent during the lifespan. In case if the agent has neuroprotective properties, we predict people who were exposed to it for a longer period at higher dosages have lower overall prevalence of PD than the general population of the same age group. Our concern is - what would be a minimum number of participants who are 60 years old or older, to be able to estimate the agent's potential beneficial effect?
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Hii Maja. In my opinion it should correspond the population of the area you are covering. Say for example, if you targeting an area with 10000 population, you should have at least 10 PD patients (which corresponds to its prevalence, i.e., 1%). Good luck
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My lab is studying neuroprotective effect towward Sh-SY5Y cells. However, when I seed the Sh-Sy5Y cells in Sigma 96 well plate coated with PDL (cls3842), 3 days later, all Sh-SY5Y cells clumped together forming small lumps. In normal, they should be divided indivudally, equally spread inside the wells. This abnormal phenomenon does not appear when we used in a 96 well plate without PDL.
It surprises me since I read papers that using SH-SY5Y cells coated with PDL before.
I am wondering have you heard of any similar observation, and do you have any suggestion to prevent this?
Or do you guys have any suggestion for how to do pdl toward plates?
Thanks!
Thomas
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Hi Di, use the HistoGrip for SH-SY5Y differentiation is super good. https://www.thermofisher.com/order/catalog/product/008050#/008050.
HAVE A TRY.
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I want to know whether there are any non invasive techniques to detect neuroprotection in humans
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Upto now no gold standard or best non invasive method to detect neuroprotection in humans are not available, but fMRI will help somehave.
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BRIMONIDINE has been used by some as a NEUROPROTECTIVE agent, for example in normal-tension glaucoma. Is there any evidence for it ?
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There does seem to be some encouraging evidence of α2 agonists as neuroprotective in contexts of ischaemic insult in the CNS. See below:
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We are learning a lot about brain inflammation causes, treatments and effects We are learning more about the benefits of neuroprotective chemicals.. Can we reverse the damage from years of harmful inflammation on the brain?
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I Agree With Isabel Taveira
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i will do my research which is testing neuroprotection of drug onglobal cereberal ischemia reperfusion model in wistar rat but i want to know the factor should i considered when i choose age and weight of the rat
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Hi Everyone. I am trying to check the neuroprotective activity of some compounds in the rotenone model of Parkinson's disease in PC-12, for which I will check the effect of that compound on cell viability first. I want to ask whether it is required to differentiate PC-12 for this purpose, as I tried to differentiate the cells using 30 ng/mL as well as 50 ng/mL NGF. I am able to see the differentiated cells in 3-4 days in 96 well plate, but NGF itself is causing cell death, which could be a variable for the cell viability test.
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Hii Suriaya. I am currently seeding 5000 cells per well in 96 well plate. I will try with 2000 cells per well for this time. Moreover, I am also getting cell death in 6 well plate, where I am seeding 5,00,000 cells per well. Please suggest if I can differentiate using less dose of NGF.
Thank you
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Can anyone give me some clear ideas how glial cells such as oligodendrocytes protect neurons? Is that only wrapping?
Thanks
Monokesh
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Monokesh Kumer Sen and Andrew Goldfine : In Neurology Today (January 24,2019/volume 19/issue 2), which is one of "The official news source of the American Academy of Neurology", there is an article on Oligodendrocytes and Multiple Sclerosis. It destroys the myth of the OCDs being neuroprotective and helping in speeding up the action potential along the axons. Apparently, there are a sub-type of OCDs and their Precursors that act as antigen presenting cells to the Immune System and thereby help in attacking the myelin of other sub-type of OCDs. These OCDs and their OPCs interact with the T cells just as the other APCs (such as dendritic cells, macrophages and other immune system cells) resulting in inflammation causing destruction of the myelin (the axons and eventually the neurons) that has been well described in Multiple Sclerosis. Here, we have cells of the Nervous System destroying other cells of the same system by recruiting the cells of another system, the Immune System! This changes the paradigm of the pathophysiology of MS and how it should be treated. It also explains why the current therapies are about 30 to 50% effective, except for Tysabri which can be up to 70% effective in some patients. I had presented the concept of the "Unity of the Nervous and Immune Systems" as being two parts of one system called "The Neuro-Immune System", at a major Medical Center in 2017, and how looking at these two systems as two parts of one results in a changing the current paradigm of MS pathophysiology and give us a new paradigm which will make finding more effective therapies for this devastating and disabling disease of young people, women more than men. However, I was laughed at for entertaining such an idea and was told that it will never be accepted because it was too outrageous! I wonder what those people are thinking after reading this Neurology Today article? thanks.
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I am a nurse who is researching why some cancer patients are not reporting the same dramatic effectiveness of high-dose cannabinoid extracts on causing tumor regression as some others. Here is the best current article I know of which explains the Anticancer Mechanisms of Cannabinoids and includes the information about THC-resistant glioma cells that overexpressed Midkine (MDK) and became sensitive to the THC after pharmacologic ALK inhibition. Velasco G, Sánchez C, Guzmán M. Anticancer mechanisms of cannabinoids. Current Oncology. 2016;23(Suppl 2):S23-S32. doi:10.3747/co.23.3080.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/
 
We know there are different rates of over-expression of CB1 and CB2 which appear to play at least a partial role but, of course, the various tumor microenvironment factors, mutations and, especially, this information about MDK/ALK as a mechanism of resistance to THC should soon produce much more clarity about this problem.
 
I am intrigued by the knowledge that Non-Small-Cell Lung Cancer and many Breast Cancers often have ALK mutation (and there are significant patients with NSLC and Breast Cancer who do not seem to get as much/any tumor regression yet others get dramatic regression and even No Evidence of Disease with high-doses of THC and CBD). The NSLC patients with ALK mutations are suddenly becoming more treatable after addition of an ALK inhibitor crizotinib, ceritinib, alectinib and others. I have been unable to find any research assessing ALK mutation status and THC resistance or sensitivity for tumors from other tissues than the brain.
 
I can't help but wonder if research could show if there are THC-resistant tumors of lung and breast ++ that are also ALK mutated or Midkine overproducers that may regain their sensitivity to THC as the glioma cells did after pharmacological ALK inhibition.
Thank you for your assistance.
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HA, I know exactly what you mean! Had similar cases and the delusory stuff is widespread thanks to the unethical "cannabiz" b.s. Would love to chat. I'm in a home office these days, based in S.Oregon ie pacific time zone. My cell is 541 326 6082. Afternoons best. Around most of the day tomorrow wed 5th but can call you to suit if you are still a busy onc nurse. Let me know what works. Best JT
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I would ask you about maintanance dose of the memantine. Was it actually only 1 mg or this is an error. Bacause simple calculations suggests a 10 higher dose.
Sincerely, Vladimir
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Actually we have initial reduction of dose. After first 12 h 20/2+1=11, next 12 h 11/2+1=6.5, 48 h later 2.125+1=3.125 and so on. 12 days more we have stable 2 not the promised 20.
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I am using EMS for mutagenesis of Neolamarckia cadamba for my fyp. My lab does not have DMSO. So I need other alternative of DMSO
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Hi Nur,
It is miscible in chloroform.
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How can I design a study to test the neuroprotective effect of a fruit using albino wistar rats?? Pls can you treat this as urgent??
Thank you for adding your ans
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We found that this drug is able to improve memory loss and anxiety and also is able to restore the expression levels of neuroplasticity genes in mice.
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How can I design a study to test the neuroprotective effect of a fruit using albino wistar rats?? Pls can you treat this as urgent??
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The experiment is for assessing plant's neuroprotective effects.
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Dear sir Franco.
Please elaborate a little more. My work is on rat's brain hippocampal slices. What will b the consequences?
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i want to test neuroprotection of drug in rat but the dose present of this drug in mice only so what should i do?
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Hi Salma Nabil,
The Rat and the Mice do not have the same LD50, so there is something to convert the dose !!
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I am currently looking at neuroprotective effects of a compound on shsy5y cells. Wanted to probe for Tyrosine hydroxylase post treatment.
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Hy,
enclosed you find an article about a study in which I used a monoclonal anti-TH from Sigma for western blotting.
Sincerely Yours
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I am working with amyloid beta peptide 1-25 to study neuroprotective effect, and before each test the peptide must be aggregated for use, I would like to know how long I can store the aggregated peptide for use in the neuroprotection assay.
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Thank you very much for your reply
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To evaluate the neuroprotective effect of a molecule against the beta peptide 25-35, in the methodology the molecule should be applied 2h before the peptide, but the molecule must be extracted from the cell culture before adding the peptide?
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Ok Dr. David Rotlant,
Thanks for your reply
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Parkin protein importaint bıomarker in neurodegenerative disease and this protein has neuroprotectıve effect in neurodegenerative disease and cancer.
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This article was about increasing parkin activity, you can check it: Ubiquitination Increases Parkin Activity to Promote Autophagic α Synuclein Clearance - Plos journals.
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Are training opportunities the main solution for the development of the field of neuroscience in poorer countries?
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Cuba may be a good to explore.
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I have a question regrading permanent MCAO. I am using rats for my experimental model by means of 4-0 nylon with rounded tip (heated manually) and I coat the nylon with poly lysine before experiment. Usually I collect a sample after 24 hrs.
Most of the rats die within 24 hours of MCAO, although there is less bleeding (I take necessary steps to minimize the bleeding) and everything goes normally. The rats awaken after the surgery but are not in a good condition and within 10-14 hours they die.
When I inspect the brain, I notice a very big infarction. Now I am worried that this is why the animals are dying.
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During the first 24-48 h of ischemia there is a huge intracranial pressure due to vasogenic edema (if you have acces to MRI images you will se a displacement of the middline of the brain. In very large infarctions edema may be fatal and rats die within 24-48 h, depending on severity.
When you are performing a transitory mcao, try to reduce alittel bit the duration of the occlusion before reperfusion (60 min as reference is fine). When you practice a permanent oclussion, try to use a slightly smaller filament.
When you reduce a little bit the size of your lessions, edema becomes serious but no fatal, and your survival rates will increase.
Furthermore, during the first 78 h animals have problems to get acces to water and food, try to change food pellets for a paste, prepared with pellet powder and water, and leave a bit on the bottom of the cages. In severe cases you may use i.p. or s.c. injections of saline to keep the animals hydrated.
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At what condition do I have to treat cells with LPS? In serum free media? For how many hours?
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Hi Sagar,
Here is the protocol I use for BV2 or primary microglia cultures:
NO assay
Prepare Griess reagent:
2.3ml Phosphoric acid (85%)
1g Sulfanilamide
0.1g Naphtylethylenediamine
97.7ml water
Vortex. Prepare Griess reagent at least half a day before use. Protect from light.
Keep media from cell cultures on ice.
Prepare standards from sodium nitrite (NaNO2): from 0 to 1000 µM. Use the culture media for dilutions.
Pipette media and standards 50µL/well on a 96w-plate.
Add 50µL of Griess reagent on top of each sample. Shake for 10min and protect from light.
Measure absorbance at 540nm in the reader machine.
Good luck,
Sighild
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Good day. I am about to conduct a neuroprotective studies of an endemic plant extracts using Drosophila melanogaster as animal model. Most of the journal articles that I have read did not use positive control but I just want to know if there are any. Thank you very much.
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It depends on the type of damage you are goingto induce and type of neuroprotection you are trying to evaluate, but I don't think the positive control is necessary in this case. As you said it yourself, most of the groups don't use one. 
Best,
Jan
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I saw several journal articles who utilized paraquat and acrylamide for neurotoxicity studies in Drosophila melanogaster. There are more studies which used paraquat but it is more toxic and more difficult to handle dispose compared to acrylamide. What are your thoughts?
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Your choice of model and toxicant depend upon the question you are asking. First define your research question or hypothesis. Then devise specific aims to test the hypothesis . Finally, choose methods to carry out the aims.
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I want to do studies on neurotoxicology or neuroprotective properties of natural products. Can you suggest doable bioassay for this? Im thinking of using Drosophila melanogaster. Any thoughts? Thank you for your help.
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There are many indirect (behavioral) assays you could use in Drosophila. Activity, courtship activity, starvation resistance, etc. I'm sure there are also histological & biochemical assays, but that is outside my experience.
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I am hoping to investigate how administration of a neurotoxic substance affects the blood-brain-barrier in the rat brain, and how a potentially neuroprotective substance attenuates this.
Could anyone please suggest an appropriate methodology for this, or point me in the direction of suitable references?
IHC/IF strategies would be highly convenient!
Thank you :) 
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What our lab has done in the past is we would inject a high molecular weight rhodamine dextran intravenously. If the BBB is compromised you will see macrophages (iba1 antibody will work nicely) pick up the rhodamine dextran. If you don't see any rhodamine dextran on macrophages it means it is intact.
I hope this helps.
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I injected a drug (subcutaneous in mice) and I noticed that there was an increase in number of microgias in the hippocampus (IBA positive cells). These microglias are more branched and non-reactive to MHC-II.
How should I interpret this increased in the number of branches and increased in the number of not activated microglia caused by a drug compared to control animals (which did not suffer intervention)? It can be interpreted as neuroprotection phenotype even if they have not suffered any inflammatory stimulus? Is it possible that microglia become more "resting" than those of the control animals that do not have inflammatory stimulus?
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There is also an excellent new paper out from Marie Eve Tremblay showing a new type of microglia (called "dark" microglia based on their EM appearance) that becomes abundant during pathological states such as chronic stress, aging, Alzheimer's, etc. They display signs of oxidative stress, but also have highly ramified, thin processes, so it sounds like they may be relevant for your question. See paper below:
Glia. 2016 May;64(5):826-39. doi: 10.1002/glia.22966. Epub 2016 Feb 5.
Dark microglia: A new phenotype predominantly associated with pathological states.
Bisht K1, Sharma KP1, Lecours C1, Gabriela Sánchez M1, El Hajj H1, Milior G2, Olmos-Alonso A3, Gómez-Nicola D3, Luheshi G4, Vallières L1, Branchi I5, Maggi L2, Limatola C2, Butovsky O6, Tremblay MÈ1.
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Sphingosine-1-phosphate1 (S1P1) regulates various molecular and cellular events in different body parts. Its expression pattern and functions are also varied dependent upon the cells types where it is expressed. Does anyone have any information regarding the effect of S1P1 in brain vasculature? Specially in ischemic condition (many paper suggests activation of S1P1 is neuroprotective in ischemic condition, however they lack the discussion on effect of S1P1 in brain vasculature). So if you have any information regarding the S1P1 signaling in brain vasculature, please do share !!!
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S1PR1 is one of the targets of the multiple sclerosis drug FTY720 (Fingolimod). Here is a review article about S1P and S1PRs: http://www.hindawi.com/journals/mi/2016/8606878/
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Could you please provide me some article which showed improvement of neurological deficit without change in infarct volume or vice versa after drug treatment flowing stroke induction in rodents.
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Just recently, features of psychiatric disorders such as schizophrenia were suggested to be due to a decrease of brain memory center’s inhibitory neurons. HSV-infection is primarily limited to mucosal epithelial cells and neurons, and autophagy is critical in antiviral defense in neurons. Given that type I IFN treatment failed to completely block HSV-1 replication and induce cell death in neurons, some xenobiotical factors might be considered triggering replication of neurotropic HSV-1, and lead to a loss of inhibitory neurons.
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So selective neural damage, mediated by activation of HSV1, would be triggered by an environmental toxin? Interesting idea, but in terms of translational research, you may have a long road ahead... HSV1 has been suggested to be the culprit in many neurological and psychiatric diseases, but so far the evidence is anything but convincing. On the other hand, there is no denying that HSV1 works in mysterious ways http://www.neurology.org/content/83/21/1888.short
J
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I'm looking for a suitable human neuronal cell line for neurotoxicity or neuroprotection screening. Which human neuronal cell model is best for high throughput screening? Can anyone help?
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Our investigations deal with the searching of antihypoxic and neuroprotective mechanisms of BDNF (Brain-derived neurotrophic factor). Previously we used an antagonist of tropomyosin-related kinase B receptor (a high affinity receptor to BDNF) - k252a, but now we would like to find more specific blocker.
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Dear Sakharnova:
I found this paper "Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice"
However, you can also check many other drugs here:
Best regards. Bruno
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What are the recent guidelines and advancement in the PD management? Please share your experiences.
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Resveratrol Stabilizes Amyloid in Alzheimer's
Pauline Anderson
| September 17, 2015  
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High doses of purified resveratrol, a polyphenol found in some foods, appear to stabilize levels of amyloid beta (Aβ) in cerebrovascular fluid (CSF) and in plasma in patients with mild to moderate Alzheimer disease (AD) and are safe and well tolerated, a new phase 2 study has shown.
Although it is too soon to start recommending resveratrol supplements to patients, the research indicates that this compound is safe and is promising, lead author R. Scott Turner, MD, PhD, professor, Neurology, and director of the Memory Disorders Program, Georgetown University Medical Center, Washington, DC, one of 21 medical centers across the United States participating in the study.
"It seems to have some interesting effects, enough to justify further research into this strategy," he told Medscape Medical News.
The study was published online September 11 as an Open Access article in Neurology.
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Our lab recently thought of an interesting potential link between a protein of interest and neuronal excitotoxicity. We thought it might be a good idea to do a pilot study in which which we induce seizures in wildtype mice vs transgenic mice and evaluate the seizure-associated apoptosis. However, we have never conducted seizure studies before and our transgenic mice are on a C57Bl6 background. I've read several reports indicating that C57Bl6 mice are resistant to seizure-associated neuronal apoptosis. I found a few articles reporting seizure-induced neuronal apoptosis in C57Bl6 mice, but those are only a few articles and the majority of publications suggest that C57Bl6 mice are resistant. For anyone with experience inducing seizures in C57Bl6 mice, will they truly have little to no neuronal apoptosis even with severe seizures? Or is there a particular drug (kainate vs pilocarpine vs others?), administration method (IP, SC, ICV, etc), and concentration that you would recommend which could stimulate enough excitoxicity to evaluate for neuroprotective effects of the transgene?
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C57bl/6 are resistant to auditory but not drug or febrile induced seizures. The morphological features of apoptosis and cleaved caspase-3 suggests C57bl/6 have quite restrictive doseresponse to seizure induction. Reference below
Characterization of neuronal death induced by focally evoked limbic seizures in the C57BL/6 mouse Araki et al  8 JUL 2002   DOI: 10.1002/jnr.10356
Kainic acid (KA) effectively elicited ipsilateral CA3 pyramidal neuronal death within a narrow dose range of 0.1–0.3 μg, with mortality <10%.Focally evoked seizures in the C57BL/6 strain associated with a restricted pattern of apoptotic neurodegeneration
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Can we adapt the strategies in brain injured patients?
In a recent pilot study, Werndle et al. presented preliminary data of a new technique for the continuous monitoring of spinal cord pressure and the corresponding spinal cord perfusion pressure (Crit Care Med 2014;42:646–655). Their analyses revealed that the use of inotropic drugs for an increase of spinal cord perfusion pressure optimizes neuronal function measured by motoric evoked potentials and muscle strengths below the spinal level of injury.
Are we ready for a routinely monitored management of spinal cord perfusion? 
Which mean arterial blood pressure should be targeted in this context?
How long and how invasive should we monitor?
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Indeed, a fascinating topic. Thank you Dr. Sutter to bring this up. I came across a recent article by the Cambridge/London group that has enormous experience with ICP. Intra-spinal cord pressure seems to be closely matched to epidural pressure at the level of the lesion in spine-injured patients, which would make pressure monitoring less invasive and still reliable. Regarding spinal perfusion pressure, the evidence being gathered is most convincing for a principle analogous to CCP.
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I know of it possessing majority of the phytochemicals but want to know whether it has proved to have neuroprotective ability or not.
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I believe that further studies should be done to evaluate the mechanisms associated with decreased reactive oxygen species (ROS).
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I have multiple breakages on my bands. I use 4% stacking gel, 10-12% separating gel, I block overnight at 4 degrees with 5% nonfat milk in TBST, 1st antibody 1:1000 overnight (santa-cruz), 2nd antibody 1:10000 for 1:30 hr at RT (santa-cruz).
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Hi Panagiotis,
I hope you resolve the problem. If not, there may be high levels of salt in your reagents.
Vinod
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Literature varies about this so I have done some pre-tests. I've done 42C for 2 hours in an incubator but Trypan Blue still show very high viability (>90%) but the cells look very much dead on microscopy. Should I be using a more sensitive assay? or the heat stres condition is inadequate?
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I would try serum deprivation.
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I'm searching for a neuroprotective endogenous product, which will ameliorate the toxic insults by LPS.
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How about docosahexaenoic acid (DHA), the major omega-3 fatty acid in our brain and other organs?
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I am having some difficulties on finding papers related to the effect of phospholipids, such as phosphatidylserine and phosphatidylethanolamine, on brain primary cultures, in terms of neuroprotection, citotoxicity and cell morphology.
Any clue?
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hope you will find what you are looking for.
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It has been seen that brain injured patients with HGH deficiency often suffer with depressive symptomology. My interest is in whether anyone has done a study on this, as this is part of a working hypothesis of mine, that HGH may play a role (through the proliferation and differentiation of stem cells) in maintaining and repairing cognitive functioning,(specifically in the areas of attention, memory) and emotions.
Another hypothesis which is linked to this, is that BDNF and HGH work together in different ways with regards to neurogenesis and neuroprotection, but that both are required to restore functioning. Has anyone done any studies on both of these factors together (there are a great deal of studies on BDNF, but none that I can find that look at both together)?
In the case of both hypotheses, I have not been able to find studies specific to what I have mentioned.
Any comments or input would be appreciated. 
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Hi Cheryl, 
I didn't study depression, but I know that GH-deficient untreated patients show it besides many other symptoms; I know too, my own experience as MD, that treating GH-deficient patients improves these symptoms. What is the reason for it? before trying to give an answer I will tell you that BDNF is one of the many neurotrophic factors induced by GH.
I don't think that correcting or improving symptoms such as depression, associated to GH-deficiency, might be due to the known GH effects on brain neurogenesis and plasticity, but related to the really complex regulation of pituitary GH secretion.
Pituitary GH release is mainly subject to a negative control from the hypothalamus. This is due to somatostatin; this peptide negatively controls the hypothalamic release of GHRH and its stimulatory effects on GH secretion. Therefore, somatostatin is the main controller of pituitary GH release.
In turn, somatostatin is mainly controlled by catecholamines, mainly noradrenaline that is formed from dopamine. High levels of noradrenaline inhibit somatostatin release, then GHRH can be released inducing GH secretion.
If you have GH-deficiency it is likely that somatostatin levels are decreased, consequently there is no need for increased catecholamines levels. Perhaps there is the answer to your question. 
If you administer GH, it produces a positive feed-back on somatostatin, leading to the release of this peptide. This, in turn would lead to increased catecholamines turnover....
While all of these mechanisms are real and we described it years ago in Trends on Endocrinology and Metabolism, my description about what could happen in GH-deficiency associated depression is only a hypothesis.
Best regards
Jesús Devesa
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In primary neuron culture, I want to test excitotoxicity of glutamate and neuroprotection of drugs. I will use alamar blue test for the cell viability. How many Div Can I do the tests?
Thank you.
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Hi Eduardo - I would definitely support Sven's comments. You can't really look at excitotoxicity properly until the neurons have developed synaptic connections and the receptor machinery of excitatory receptors has been well localised to receptor complexes. We published on this issue a few years back. You may see excitotoxic effects due to potential extrasynaptic receptors at earlier stages of development. See https://www.researchgate.net/publication/6929998_Localization_of_glutamate_receptors_in_developing_cortical_neurons_in_culture_and_relationship_to_susceptibility_to_excitotoxicity
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Im trying to conduct a neuroprotective assay with SH-SY5Y cells differentiated with RA and TPA to dopaminergic neurons. 
There seem to be multiple cell lines capable of similar feats, and some that seem to be used more without differentiation.
Is there any reason to go through the trouble of dual differentiation? or would it be easier and more reliable/reproducible to work with N2A/CATHa/PC12 cell lines, as they seem to be the standard in neuroprotective research. 
I understand that SH-SY5Y cells are of human origin, but even still, they dont seem to be heavily used when compared to mouse line.
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Hi Kelly,
In our lab we are using SH-SY5Y cells for PD research. N27 rat dopaminergic cell line is another choice of ours. However, I think, one of the best options you can use is the primary midbrain cultures isolated from rat embryos. We dissect midbrain from E17 rat embryos and culture the cells. It's, obviously, a mixed culture including dopaminergic and GABAergic neurons, as well as astrocytes and microglia. You can also inhibit the growth of glial cells in cultures dishes via different treatments if you wanna eliminate these. Since it's a mixed culture, you can see the effect of your treatment/chemical/compound on different neuronal or glial cells, which might be an advantages depending on the purpose of your neuroprotective assay.
I hope this helps a bit. Good luck!
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Luciferase activity assay showed highly significant binding of my drug to androgen receptor, I am planning to do IHC and see whether androgen receptor is over expression in OVX  female brain  after drug treatment elucidated AR dependent neuroprotective pathway in female in absence of estrogen.
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AR is highly expressed in brain tissue. I would not be surprised there if there would be a reason for that. I am happy to learn with you if there is somebody that is willing to share info with us.
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Thank You in advance.
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The question posted is How to calculate the effective dose of a particular compound in rats?
By definition, an effective dose is the dose of the compound or agent at the target organ that has an effect at the target organ.  By your question, I presume that you do not have a means of measuring the dose of the agent or compound at the target organ that produces the effect of interest and therefore, you are looking to "calculate" the dose at the target organ.
Where appropriate pharmaco-kinetic models exist for your specific rat species, you might use them to calculate the dose at the target organ.  Such models presume that you can model the distribution and fate a compound or agent under certain conditions within the rat, but often fail to account for specific protein binding, selective or active transport, and other processes that might be specific for the compound or agent of interest.
In toxicology, scientists have devised several means of estimating the "effective dose" at the target organ from various dosing protocols (e.g., oral gavage, consumption of food or water, percutaneous injection, dermal absorption, etc.). Such estimates, while useful, often rely on assumptions that may or may not hold true for your species of rat (e.g., body weight, pharmaco-kinetic differences, etc.). Roughly, toxicologists are generally interested in the concentration of the compound or agent in blood over time, with the area under the curve (concentration v time) describing the estimated dose to the target organ.
To appropriately answer your question, I would need to know the compound or agent administered, the species of rat, the target organ and effect of interest.
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I'm trying out a new neuroprotective substance on animal models of ischemic stroke, so far I could prove that this particular thing could cause caspase 3 activity to decrease at 24h of reperfusion. But my boss wants to see if it also affects other forms of cell death/damage during this time period. From the papers that I've seen so far, 24h to 72h is a pretty nice time span to see apoptosis, too early for autophage and too late for excitotoxicity. Does anyone have any suggestions on where I should look or what papers I should read?
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Due to my experience with neurorehabilitation of patients after long-term coma with the following outcome in the apallic syndrome or in vegetative states, we observe the minimal brain electrical activity similar to serow line activity or dominant delta-wave activity with convulsive activity. We connect this brain damage not only with brain hypoxia, but also with severe ischemia, oedema and venous stasis in the brain tissue. We had a good result of the intensive medicaments treatment combine with intensive rehabilitation - the restore of the conscience, speech, memory, active moves of limbs etc. More - http://inno-health.com/istoriji-uspihu-roman-shvorak/ and http://angio-veritas.com/technologies/nejroreabilitatsiya-psyhonevrolohichnyh-hvoryh/apalichnyj-syndrom/?lang=en
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I would like to know in context of Parkinson's disease?
I would like to know whether I should worry about using ethanol as a solvent for testing neuroprotective effects of various agents (especially in parkinson's models), because of its inherent protective effects (lets ignore the vehicle control for now). 
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Dear Colleaque,
My experience has shown that in rodents ethanol as a solvent of medicines has mainly protective effect. In particular, ethanol reduces oxidative stress of brain tissue arising from MAO-dependent oxidation of dopamine.
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As T3 has a positive influence on axonal growth, dendrite branching and development of myelin sheath I wonder if it could be used to increase the regeneration processes in post stroke patients.
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Like Pablo said, I think Mdzinarishvili A. et al has done a similar study quite recently. However, I believe that they give T3 30 minutes BEFORE t-MCAO rather than afterward which makes it potentially less clinically relevant. It would be nice if someone looked at it after stroke. You'll have to excuse my unfamiliarity with T3, but for the reasons you've given, it would be even better if someone delivered T3 at a later phase (during repair phase, for example) to see if it helps in the recovery process. 
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Currently I am working on a systematic review with meta-analysis. I will be writing review about the neuroprotective efficacy on a drug. From the extracted papers I collected infarct volume and neurobehavioral score. But now I am facing a problem, some of the results are in mean +/- SD format (7.24 ± 1.04 versus 12.59 ± 1.44mm3) and some are in percentage improvement (47.07 +/- 7.63% versus 26.27 +/- 5.63%). Is there any way I can combine these data to find out effect size and plot a graph? If yes, could you suggest a method or software?
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I agree but would also recommend having a look at the fantastic meta-analysis package metafor for R, which includes a function to calculate effect sizes from different indicators (escalc()
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I am studying gender differences following cerebral ischemia, and i have surprisingly noted that NSPCs donot express BDNF after 7 days of ischemia. I performed IHC and co localization studies with Brdu . Has anybody seen the same expression pattern of BDNF? 
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1) As we all known, in clinical trials,the NMDAR antagonists show prominent neuroprotective effect. However, all of them failed in clinical trials.
2) Why should t-PA should be used within 4.5h?
3) Cortical neurons can be more resistant to hypoxic injury than microglia in a relatively short period according to our own observation.
I am thinking that should a neuron-glia protective strategy should be more reasonable in stroke since that more and more functions exerted by glial cells have been found.
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Dear Lee, The clinical trial on NMDAR antagonists show failed it may be due to the randomized mixed population and moreover, I don't think the stroke can be prevented by single target. Always should go for computational therapy. As we all know there are so many drugs and reports showing protection by inhibition of different molecule through different reagent or compound in ischemia. Then how could be possible prevents ischemia by one target like NMDA receptor.
Secondly t-PA with acute ischemic stroke, why it is three-hour window because after three hours of ischemic condition goes to more damage of brain becuase it is not now the acute ischemic stroke, Its a severe and cause intra-cranial bleed and more intravenous thrombolysis.
Third, in case of sensitivity of neurons towards ischemic damage is less because glial cells initially protects the neurons in pathological condition.
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Many literature says that antioxidant system does not play role in neuroprotection in female brain after an ischemic stroke, ROS is generated after stroke in both male and female brain, then how is the neuroprotection observed in female post menopause, has anybody studied any antioxidant enzyme in female brain? Also is there anybody using non-hormone based molecule in female following stroke?
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As far as i know, there is no discernible difference. often in studies they will use one sex over another (in rats, typically female....just easier to handle). As Just mentioned, there is an influence of estrogens (and related hormones), but not a significant one to justify using it as a  pharmacological target.
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I have no experience whatsoever transfecting cells with cDNA, and I am looking for help/guidance/knowledge from the community.
What electroporation unit do you recommend? I will be using mainly PC12 cells.
Are there particular settings or solutions you like?
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All good over here, don't mind if I answer my own question.
We bought a Biorad electroporator and have gotten good results thus far.
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If so, you might be interested in our development of such future devices.
We are a university group and think about starting a company in future. Don´t worry, this is not an advertising or so, I do not want to sell you anything.
We would just like to cordially invite you to take part in a very short poll to get very first impressions of the academics´ and other professionals´ needs.
Please answer six short questions regarding the academic and the pharmaceutical version we have in mind. This takes just five minutes of your time per poll.
For you convenience, you can use the following two survey links:
For the ACADEMIC system (LOW throughput, SEMI-AUTOMATED):
For the PHARMACEUTICAL system (HIGHER throughput, FULLY AUTOMATED):
Let´s shape the future of patch clamp analysis together! You are free to leave your personal data, if you would like to test our prototypes in future (2-3 years)! You can visit our university project site on the following website link:
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Hi Gabriele,
the mentioned nanion products do not allow for the analysis of cellular networks. This product family and ALL other APC systems availbale were developed and optimized for cells in suspension, cells freshly detached from culture flasks or cells from thawn vials. These APCs cannot analyze cultured cellular networks and were not built for that issue. Let me know if that´s not right.
Don´t get me wrong, nanion and the other APC producers did a great job with their APC development. Chapeau! The devices are great if you need higher troughput. I guess the new nanion 384-channel machine will have a good response in the market. Congrats to nanion!
But if you need network data or a higher organisation grade like in a cell network (some ion channels are only expressed when the cells are attached to a substrate or to other cells...) or in a brain slice, you are limited to manual patch clamp. And we all now that using a manual rig does not allow for higher throughput (5-20 data points per day if you are very experienced). Hence, we believe (and know from our potential customers already) that our future systems are complementary to conventional APCs. Further, our system will drastically increase the parallel number of patched cells, up to 16 at once with one chip! If we get that done: world record! I am sure that the information of the cell-cell-communication analyzed with our systems will be of very high value in future.
By the way, Prof. Markram´s 1 billion € project uses a 12-channel setup (http://www.2045.com/news/31235.html). The rig can be seen in the last figure in this article. The parallel patch clamp of neurons is an important tool for his research.
Well, with our short survey we would like to know the point of view of scientists regarding our technology to define our product development when we start our company in future.
For further information, please contact me under philipp.koester@uni-rostock.de
Best regards, Philipp
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I'm only either finding pharmacological/small compound inhibitors or cytokines that activate more than STAT3.
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Hi,
The Tocris company offers a STAT3 activator polypeptide with some interesting properties including CNS penetration and low systemic toxicity, called colivelin. Seems to be rather specific.
Good luck!
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We have used the model of four soft knots on the sciatic nerve and the model of four soft knots on the saphenous nerve, but were unable to generate the expected hyperalgesia. Animals exhibited no significant changes and sometimes presented hypoesthesia.
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It depends upon what you want to investigate and your expertise. Several "good" models of sicatic nerve lesions have been used to study neuropathic pain, and most are useful. Particularly the spared nerve injury is probably the most consistent in terms of results. What is also very important is to use adequate methods for evaluation. I would not recommend the hot plate. Algesimetry tests for mechanical (Von Frey) and thermal (plantar) focal stimulation are adequate. However, you have to be aware of the innervation territories of the limbs and which areas are denervated or innervated in the surgical model you use. You may take a look at our recent article Cobianchi et al Exp Neurol 2014, 255:1-11.
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And neurodegeneration in mice.
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There are multiple ways to assess neuroinflammation. You can perform immunohistochemistry by using specific markers for microglial activation (Iba1) , astrocytic response (GFAP), and neuronal loss (NeuN or Fluorojade for dying neurons). You can also look at the levels of various cytokines that are upregulated during inflammation (TNF-alpha, Interleukins, TGF-beta, and so on).
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Does neuroinflammation and neurodegeneration induced by continuous infusion (intracerebroventricular) of LPS occur in all CNS neurons or only in specific regions? The literature is rich in research about the hippocampus, but not on other regions. I have special interest in the hypothalamus.
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As you know LPS mediated inflammation is closely associated with nitric oxide production and up regulation of iNOS production at most sites all of which has considerable publications documenting LPS effect on inflammation. Other mediators also play a role. Systemic administration of LPS also produces change in the Nucleus Tractus Solitarii. There is a lot of literature supporting communication pathways between the immune system and brain. I have attached one for your consideration. You are treading on unknown territory as best I know and very interesting work, I look forward to hearing more.
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How to carry out In-Vitro evaluation for Alzheimer disease (both cell line and enzyme inhibition assay)?
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There is many factor that simulateneously involved in AD. To check these you must go with antioxidant, AchE, LOX, Amyloid Protein cell line protection assay, serotin assay and many more in vitro assay.
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Substantia nigra.
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To locate any small brain part, first you have to under stand the rat brain atlus in coronal sections. The main part on the coronal section is the varying size of the hippocampus. Hippocampus starts from the optic chiasmaa in small size and as the sections proceed to posterior it goes down and down and make a complete half ring or comma like structure on both side of the hemisphere. You may easily locate the position of the substantia nigra. The rats brain atlus and abbreviation used for the substantia nigra has been pointed out by Dr. Sushil Kumar.
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I have been trying to test the toxicity of Amyloid beta oligomers on neurons by measuring ROS. I am observing that the ROS response on exposure to these oligomers is highly variable when tested even in consecutive experiments as well as with the same oligomer preparation. I tried to characterise the oligomer preparations on Tricine gels which I found to be consistent every time. I want to ask what factors can be there behind this variable response and how to reduce them. Is it also observed by other researchers working in this field?
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Thanks Jeffrey. I need to sincerely think on your points.
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Transforming growth factors, Activin receptor like kinase
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Neuroprotection is a contemporary approach used in the treatment of glaucoma, retinitis pigmentosa, diabetic retinopathy.
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Dear Marianne, we have been studying retinal diseases for a few decades and in the last decade, have developed the use of save, non-invasive therapies with no side effects reported. These are dietary saffron and near-infrared light therapy. See my publications for example. I'm under Prof Jonathan Stone's group at Sydney Uni and he is the brains behind these studies using saffron and infrared light therapy for AMD, retinitis pigmentosa, Parkinson's disease and Alzheimer's disease. These therapies are said to be protective by reducing oxidative damage and switching on mitochondrial protective pathways.
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I am asking this with respect to resuscitation from cardiac arrest. Usually autoregulation to CO2 is impaired in this situation. Therefore, if hypercarbia is neuroprotective, what is/are the mechanism(s)?
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Permissive hypercapnia may induce augmented cerebral blood flow in the situation of relative low-perfusion pressure after resuscitation from cardiac arrest could have
beneficial effects to the globally ischemic brain.
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I also have a problem with detecting the LC3II band on my western blot. The lC3I is not well separated from my LC3II band or the LC3II band is a smear.
I use 4-20%Tris/Glycine gels from Biorad. For the lysis step we use MPER extraction buffer with proteinase and phosphatase inhibitors. I use 75 Volt for the SDS-running, 35 Volt for the transfer time. I also use PVDF membranes. But I do not know if I should change the running, transfer buffer or the lysis buffer for the sample preparation?
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Hi Natascha, I use homemade buffers for running and transfer, the lysisbuffer is a simple Tris-EDTA-TritonX mixture (pH7,5) with proteaseinhibitor cocktail from Sigma (you can find the lysisbuffer recipe on the Abcam homepage). My antibody is from Cell Signalling LC3B (D11). Check out the publication in Autophagy 3:6, 542-545; November/December 2007 about how to interpret LC3 Immunoblotting, it is very interesting. Make sure that your protein hasn´t travelled too far (prestained marker - any company will send you a testsample, if you do not have any at hand) and maybe try another antibody (other company). I would also give it a try with a high percentage homemade gel, Valeria also uses 13-15% and it is not that much work to pour a gel. What about your transfer, can you detect the marker on your film and is your stack packed tightly (I once had a smear when I didn´t have a tightly packed stack), do you check transferefficiency with a reversible stain? (I use MemCode from Thermofisher) What do you use for blocking, I blocked once with milkpowder and did not get any signal from that blot and do you expose for a long enough time, one of my blots gave good signals only after 8 hours of incubation!
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Hi every body. If someone is working on the 2 Dimensional gel electrophoresis (2D) USING tissue sample, i have some question regarding focusing step. the focusing result of pH 4-7 give clear spots while with pH 6-9, spots are mostly blurred not clear. Also the region of pH6-7(in pH 4-7 IPG strip) showing no spots while their are in abundance of spots in the reaming gel. similarly the region pH rangining 9/8-9 in ( in pH 6-9 IPG strip) is also blank with no spots while the reamining gel is full of spots..Your worthy suggestions will be greatly appreciated.
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The basic region is always more difficult to focuse. I think you use a standard protocol with destreak or other chemicals that improve focalisation ?
Maybe you should as well be careful with the quality of strip (storage and limit date) and the quality of sample (no salt, etc...).
The IEF program has to be adapted as well for basic region, in order to limit the passive rehydratation step, to limit acrylamid degradation during too long steps...
(to find more details, see my last publication in Proteome science)
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I saw some articles have used DMSO and some used ethanol as the solvent for estradiol and was wondering which should I chose and how does it make a difference to my results?
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It depends on how you are going to use your estradiol and for what purpose. As long as estradiol is able to form hydrogen bonds with your solvent, you should be able to use it but keep in mind that the solvent will stay in your prep.
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I came to know that certain hippocampal cell lines don't express estrogen receptors (such as HT22). I was thinking of working on rodent cell line SCR022, but no information about the presence of estrogen receptors in it. I would really appreciate if you could help me on it. Thanks.
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HT-22 (mouse hippocampal neurons) seems to be capable of expressing estrogen receptors as evidenced by:
"In order to obtain data regarding the interaction between RyR and ERβ, we examined co-localization patterns of both proteins in intracellular compartments in the neuronal cell line HT-22. While initially thought to be free of functional endogenous ERs [45], the HT-22 cells were found in recent studies to express both endogenous ERβ [30] and ERα [46]".
ref: Rybalchenko V, Grillo MA, Gastinger MJ, Rybalchenko N, Payne AJ, Koulen P. The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+. J Recept Signal Transduct Res. 2009 Dec;29(6):326-41. doi: 10.3109/10799890903295168.
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Affiliation: SOFA (Sarcopenia & Osteoporosis Fraction in Ageing)
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The pathophysiological basis of primary open-angle glaucoma and the factors contributing to its progression are not fully understood. The elevation of intraocular pressure (IOP) is the most important risk factor, and IOP reduction is currently the only evidence-based treatment.
However, some patients develop glaucomatous neuropathy without ocular hypertension. Moreover, some patients keep progressing even with low levels of IOP. Thus, other factors may be involved in the development and progression of glaucoma.
Do you recommend/prescribe anything besides lowering IOP for your glaucoma patients (Ex: nutrition, curcumin, ginkgo biloba, sports, etc.)?
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The answer to the question “Do you recommend anything besides lowering intraocular pressure for your glaucoma patients” is complex. Glaucoma is a misunderstood disease. Until we fully understand the disease we can’t cure it. Even the role of lowering of IOP is questionable especially in NTG, why to worry about adjuncts to lowering of IOP until we fully understand this disease. We can’t treat a disease unless we fully understand it. In glaucoma we don’t even know what actually is happening to the nerve fibers. Are the nerve fibers really being atrophied in glaucoma? All we hear is that nerve fibers are being damaged in glaucoma. But word damage is very broad. What kind of damage we are talking about? Are the nerve fibers being compressed, crushed, sliced, severed or anything else. With all the recent technology we even can’t answer with certainty above basic question of glaucoma.
Lowering of the IOP in glaucoma may be slowing the disease at its best but surely unable to halt it. Therefore, it appears we are following a wrong path in glaucoma. We are following a 150 –year old paradigm of cupping without even fully understanding the phenomenon of cupping or excavation occurring in the glaucomatous disc. Ironically, we are using the term cupping to describe both physiological as well as pathological cupping. It is unheard of using the same parameter in describing both the healthy and disease state of an organ in other branches of medicine as we do in glaucoma. No wonder why the term cupping and cup/disc ratio has produced a conundrum in the glaucoma diagnosis.
Glaucoma is defined as optic neuropathy implying that nerve fibers are being atrophied in glaucoma. Optic neuropathy is big umbrella term which includes hundreds of diseases in which optic atrophy is occurring. Is glaucoma also an optic neuropathy? We must not ignore the very important fact that glaucomatous field defects reveal that nerve fibers are always being destroyed in a specific sequence starting with peripheral fibers, then arcuate and ending with central. It is unlikely that raised IOP acting directly or via ischemia would always cause atrophy of nerve fibers in a specific pattern and not destroy the nerve fibers haphazardly. If we believe that RGC’s are the primary site of injury in glaucoma then this scenario becomes even more puzzling. How is it possible that raised IOP or in fact any pathology directly or indirectly will always destroy systematically those RGC”s first which serve the peripheral vision and not occur randomly? I have been puzzled by aforementioned question in my entire professional career spanning over 50 years. But now I may have answer to this puzzling question at least to my satisfaction.
I learned very interesting things by comparing the morphology and histology of the glaucomatous disc with the non-glaucomatous optic atrophy such as due to multiple sclerosis. Morphology and histology of the glaucomatous and non-glaucomatous optic atrophy are distinctively different. Glaucomatous disc is excavated whereas the non-glaucomatous atrophic disc is non-excavated and flat. Blood vessels are sloping/ kinking at the disc margin in glaucomatous disc but not in the non-glaucomatous optic atrohies. Wedge shaped defects in the retina are present in glaucoma but not in non-glaucomatous optic atrophies. Histology of end-stage glaucomatous disc resembles an empty bean-pot devoid of nerve fibers, whereas in non-glaucomatous optic atrophies the nerve fibers though shrunken are still present.
Sloping/kinking of blood vessels at disc margin in the glaucomatous disc, prior to any change in contour of physiological cup, suggests that optic disc may be sinking in glaucoma. Excavation or empty spaces occurring in the glaucomatous disc can only be explained due to severance of the nerve fibers, not due to their atrophy. End-stage glaucomatous disc may not be 100% cupped atrophic disc but a crater left over after severance of all nerve fibers. Wedge shaped defects in the retina and arcuate field defects in glaucoma can only be explained by severance of the arcuate fibers, not by their atrophy. Progressive thinning of the RNFL can only be explained by continuous severing of the nerve fibers in the glaucomatous disc and it is not occurring in non-glaucomatous optic atrophies. In view of aforementioned I hypothesize that nerve fibers are being severed in glaucoma due to sinking disc. If true, then glaucoma is in fact a herniation of the disc in the scleral canal, a mechanical failure. In this regard the lowering of IOP may be too late. Lowering of IOP may serve as a prophylactic treatment but not an ultimate treatment if disc has started sinking and glaucoma has been initiated. We may have to find ways to stop the further sinking of the disc. Analogy: statins would prevent the build up of plaques but if the plaques have already formed then cardiologists would either break the plaques or bypass them by surgery. Thank you.
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Animals injected IP with my specific chemical end up being protected from perinatal cerebral hypoxia-ischaemia. We have clues about the molecular mechanism, but I would like to know whether the drug itself gets into the brain at all or whether it is a metabolite or secondary effect that is protecting? Is my only option trying radiochemistry?
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there is little more add. You need to take your compound's formula and synthesis to a radiochemist. They can advice you on potential pathways.
11C has only a half lifetime of 20min. you can analzye it for a few half life times. Nice thing is that if you compound comes with methylated groups, it is a natural fit.
Talk to a chemist on this one with your data, formula etc. We have hit about the limit on how to go forward without knowing more specifics.
If you employ radio methods, you will discover how powerful they are as a tool. It is almost magic what you can do compared to traditional methods for tracing compounds due to the extreme sensitivity and ease of detection.
There is a lot of infrastructure required, but there are experts and labs around to support you.
Best
Marko
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Many models out there but which is the best for neuroprotection studies? I have some compounds validated using in vitro assays and I am looking for collaborators to test them in other models.
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Hi Nat. I agree with Yannick that the main problem with AD models is their lack of neuronal death. However, if you first want to check that your drugs work by reducing amyloid burden, you can use any of the AD models. 5xFAD animals are ok to have quick preliminary results since their pathology stars around 1.5 months, althogh sometimes it's a model too aggresive to be able to see any difference. You can also try with double APP/PS1 (pathology at 6 months) or Tg2576 animals (9-12 months). As suggested before, 3xTgAD animals are a good option because they have some cell death. We have all of these animal models and also type 2 diabetes and prion animals, just in case you want to check whether your drugs also work in other protein misfolding disorders. Best, Ines.
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If blood glucose levels are further or strictly controlled up to lower level of normal blood sugar range, Can evoked potential changes be restored?
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Actually my thesis work concluded that brainstem auditory evoked potential are affected significantly in type 2 diabetes irespective of current blood sugar level / disease duration. now i am planning to do research on topic of question. but i am not getting any good research on this topic. what do you suggest sir?
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I want to use P12cells as a material to study the effect of A on neuroprotection. What are P12cells relative to neural cells?
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I suggest you do not use them. I have performed neurotoxicity experiments on human neuroblastoma SH-SY5Y cells (PC-12 are from rat and more transformed respect to SH-SY5Y) then I have repeated the experiments on rat embryonic DRG neurons and results have been different. Rat embryonic DRG naeurons are a very good model to study neurotoxicity.
Good luck.
Gabriella
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What product would be best for concentrating peptides and proteins from cell culture conditioned media? I need to concentrate about 100x without molecular-weight exclusion.
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If you have a Speedivac or like machine, that will do the job without too much trouble. You can then resuspend in your media of choice to desired volume.
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Do you have any articles regarding the protective effect of Terminalia chebula on the glutamate induced toxicity to the neurons? Both in vitro and in vivo paper will be appreciated. Either the extract or the active principle from the T. chebula.
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Thank you sir for your answer. I would be very happy if you can provide some published references regarding the neuroprotective effect of Haritaki against glutamate induced toxicity...
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