Hanna Lindgren added an answer:Does anyone know how to deal with reduced motivation in the accelerating rotarod test?
We are currently using the accelerating rotarod test to assess vestibulomotor functioning following experimental brain injury in rats. In this regard, we have encountered that it can be very difficult to motivate animals to run on the rotarod: Some animals jump off the rod after a few seconds, whereas others seem to develop a strategy where they deliberately ‘fall’ off the rod in a more or less convincing manner after a relatively short time interval (e.g. 30 seconds). In both cases the performance/score does not appear to reflect the true vestibulomotor functioning of animals, and the performance of some animals vary significantly from trial to trial.
In order to establish a baseline performance level we have been giving animals 10 trials (5 days of 2 trials) before injury. Subsequently animals have been tested on the rotarod for 7 days (2 trials per day) post-injury. We are using a commercially available rotarod from PanLab/Harvard Apparatus (fall height 21 cm, rod diameter 60 mm, acceleration 4-40 rpm over 2 minutes).
If anyone has had similar experiences and has any ideas or advice on how to increase motivation in the rotarod test, it will be highly appreciated.
I usually train my rats for three to four days prior to surgery. I use a similar rod as yours and it is set on acceleration 6-60rpm in 5 minutes. They usually start at 150s and when trained, they stay on the rod for about 200-220 s. After the lesion, the average time is approx 130s but it varies a lot between rats so the best way of analysing data later on when testing drugs/treatment is to calculate improvement from each individual baseline.
I have only been testing females whereas another colleague is using males and it seems like the female rats are more easily motivated. However, if a rat doesn't want to run on the rod prior to surgery, it will most likely not do it after either :-).
Let me know how everything goes and good luck.
Raoul Christian Sutter added an answer:Can anyone recommend a validated observer-rated pain scale for nonverbal adult patients with a stroke/brain injury?
The setting is a neuro rehabilitation unit, patients aged 18 years and up. Thank you for your help.
Dear Krystal, perhaps this link and the attached paper will be of some help...
Christopher Daniel Duntsch added an answer:Does anyone know the half-life of leupeptin?
I would like to test leupeptin by injection intraperitoneally into rats who have received a brain injury, but need to know the half-life in order to determine the best dosing time-points. Any insight would be much appreciated!
While I am not an expert in the various biospaces around this question, I do have significant experience in related animal models, drug delivery and biopharma, and models of neuropathology that include neurotrauma among several others.
A summary of the literature (at a glance) as best relates to your question follows.
Several manuscripts are listed with diverse and various reports of some relevance to the question.
For all listed below, both citations and abstracts are provided (and where relevant selected text sections).
Where possible, manuscripts of interest and relevance are attached as full text pdfs.
Feel free to email me directly to discuss, regarding approaches to these issues and questions, relevant protocols, relevant drug delivery routes and biopharma, and models of neurotrauma in rats and other small animal models.
This is a complex question, and this is even more complex to answer definitively.
If one expands the answer to include a discussion of sorts, with several relevant (some direct, most indirect) areas of research and development to reference from, what is provided is background, context, relevant examples and methods, and a foundation from which to better understand both the question and the answer.
Considerations, comments, caveats, related literature.
Mechanisms of creating cortical and subcortical (neurotrauma) brain trauma in rats (and murine models). Related models of spinal cord trauma, and models of trauma to the peripheral nervous system.
Understanding neurotrauma … cortical, subcortical, spinal cord, peripheral nervous tissue pathology and pathophysiology ... at the animal, system, organ, tissue, cell complex, cellular, and subcelluar, and intracellular level (i.e., functional, neuro- and electrophysiologic).
Modeling neurotrauma in small animals. Several approaches. Most are standardized and routine at this time. Meaning … models, protocols, time points for assessment and observation, types of data and analysis of outcomes collected routinely or as part of an experiment, etc.
Relatively complex biology, biochemistry (in vitro and in vivo), and physiology / pathophysiology relevant to studying leupeptin bioactivity in vitro and in vivo, makes the question and answer a bit complicated. Rat and murine models of leupeptin biopharma with intraperitoneal injection, in local, vascular, organ, and / or systemic bioavailability and bioactivity studies, do exist, but are diverse and not directly related to the question.
Physical chemistry, general chemistry, biochemistry, etc., of intraperitoneal fluid vs. leupeptin vs. leupeptin in a peritoneal milieu are relevant. Estimated or demonstrated bioavailability of leupeptin to the portal venous and systemic vascular system, to the liver as a first pass and bioactive organ (at the tissue, cellular, and subcellular levels), and to various systemic organs, are important, and have been studied in various models, and through many approaches.
It appears that direct measurement of the compound itself (physically), in dose and time kinetic assays, in any context, is difficult, and is not the approach used in the present (much less the last four decades). Instead, bioassays of leupeptin activity in targeted organs, tissues, cells, organelles, enzymes, functional proteins, biofluids, and other types of complex biology (in models of health vs. disease models of interest), provide a direct or indirect, relative, or cross referenced, estimate of leupeptin levels via bioactivity, in dose and time kinetic studies, and in biotherapeutic studies. Bioactivities can be cross referenced initially, routinely, or as needed, directly to actual levels of the compound with standard biochemistry and molecular biology assays.
Blood brain barrier physiology … relative to charge, hydrophobicity, size, etc, of leupeptin, relative the dose dependent biologic response (effective therapeutic dose needed in all biologic contexts) for treating or preventing a given disease or pathology such as neurotrauma (the effective dose needed ). Further, the same is true when more sophisticated approaches are used to overcome brain barrier physiology and drug delivery challenges, such as drug formulation, biopharma carriers and complexes (proteins, lipids, mixed biocompounds, etc.) ... that have better bioavailability (locally, systemically, at the blood brain barrier, etc.) … or that have some relevant gain of function (such as cortical membrane / vascular interface protein channel activity, receptor uptake mechanisms, etc. ... i.e., transferrin).
Examples for Review (Attached as full text PDFs)
Castillo et al. (2013) Measurement of autophagy flux in the nervous system in vivo. Cell Death and Disease. 4:e917: 1 - 11.
Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings. Keywords: Autophagy; adeno-associated vector (AAV); microtubule-associated protein 1 light chain 3 (LC3); nervous system; autophagy flux
Ezaki et al. (2011) Critical Review Peroxisome Degradation in Mammals; Morphological and physiological aspects of peroxisomes. ￼IUBMB Life, 63(11): 1001–1008.
This review summarizes the historical aspects of the study of peroxisome degradation in mammalian cells. Peroxisomes have diverse metabolic roles in response to environmental changes and are degraded in a preferential manner, by comparison with cytosolic proteins. This review introduces three hypotheses on the degradation mechanisms: (a) the action of the peroxisome-specific Lon protease; (b) the membrane disruption effect of 15-lipoxygenase; and (c) autophagy that sequesters and degrades the organelles by lysosomal enzymes. Among these hypotheses, autophagy is now recognized as the most important mechanism for excess peroxisome degradation. One of the most striking characteristics of peroxisomes is that they are markedly proliferated in the liver by the administration of hypolipidemic drugs and industrial plasticizers. The effects of these substances were fully reversed after withdrawal of the substances, and most of the excess peroxisomes were selectively degraded and recovered to a normal number and size. Autophagic degradation of peroxisomes has been examined using this characteristic phenomenon. Excessive peroxisome degradation that occurs after cessation of hypolipidemic drugs has been extensively investigated biochemically and morphologically. The evidence shows that the degradation of excess peroxisomes and peroxisomal enzymes is inhibited by 3-methyladenine (3-MA), a specific inhibitor of autophagy. Furthermore, in liver-specific autoph- agy-deficient mice, rapid removal of peroxisomes was exclusively impaired, and degradation of peroxisomal enzymes was not detected. Thus, the significant contribution of autophagic machinery to peroxisomal degradation in mammals was confirmed. However, the important question of the mechanism for the selective recognition of peroxisomes by autophagosomes remains to be fully elucidated.
Peroxisomes are the organelles found in almost all of the eukaryotic cells and are generally spherical in shape and surrounded by a single membrane (1, 2). The characteristics of abundance, size, and appearance of peroxisomes, as analyzed by electron microscopy, vary considerably. The use of three-dimensional (3D) reconstruction has revealed that the organelles in regenerating liver are pleomorphic with a marked variation in size that ranges between 0.1 and 0.8 lm in diameter and are distributed randomly in the cytoplasm. The evidence shows that most peroxisomes are elliptically shaped by random sectioning. Nevertheless, dumbbell-shaped peroxisomes may also be found in electron micrographs. By the use of serial sectioning, two to five peroxisomes were found interconnected with each other via narrow hourglass-shaped bridges forming a reticulum (1,3). Peroxisomes were first defined biochemically by de Duve as an organelle containing various oxidases including acyl-CoA oxidase, glycolate oxidase, urate oxidase, alcohol oxidase, etc. These oxidases reduce oxygen to hydrogen peroxide at the expense of the oxidation of the substrates. In addition, peroxi- somes also contain a large amount of catalase, which reduces hydrogen peroxide to water. It appears that peroxisomes are well adapted for the reduction of any suitable donor peroxides that may be supplied to them (2). The peroxisome concept has been established deductively by analysis of the results of enzyme distribution studies, and the name ‘‘peroxisome’’ refers to the hydrogen peroxide metabolism (2). In addition to various oxidases and catalase, peroxisomes also contains enzymes involved in the b-oxidation of long-chain fatty acids (3). The most conspicuous structural component of the peroxisome is a dense core, which has been described as crystalline, semicrystalline, crystalloid, or maltilamellated, mostly on the basis of electron microscopic images and is made up of regu- lar striation with a honeycomb appearance (2). Biochemical anal-yses showed that the structure was made of urate oxidase (4, 5). Peroxisome deficiencies participate in a variety of pathologies, including Zellweger syndrome. Their involvement ranges from a central role in several metabolic disorders to poorly understood responses to inflammatory and malignant diseases (6).
Hausnera et al. (2014) Inhibition of calpains fails to improve regeneration through a peripheral nerve conduit. Neuroscience Letters 566: 280–285.
Intramuscular injection of the calpain inhibitor leupeptin was found to promote peripheral nerve regeneration in primates (Badalamente et al., 1989 ). Direct positive effects of leupeptin on axon outgrowth were observed in vitro in related studies (Hausott et al., 2012 ). In this study, the Calpain inhibitor leupeptin was locally applied to transected sciatic nerve of rats. In this study, we applied leupeptin (2 mg/ml) directly to collagen-filled nerve conduits in the rat sciatic nerve transection model. Analysis of myelinated axons, retrogradely labeled motoneurons, and functional ‘CatWalk’ video analysis, did not reveal significant differences between vehicle controls and leupeptin treated animals. Axon number and myelination did not significantly increase 3 months after lesion induction. No difference in behavioral tests were found of significance after nerve regeneration. Therefore, leupeptin does not appear to improve nerve regeneration via protease inhibition in regrowing axons or in surrounding Schwann cells following a single application to a peripheral nerve conduit (and suggesting indirect effects on motor endplate integrity if applied systemically).
Arancibia-Carcamoa et al. (2009) Ubiquitin-dependent lysosomal targeting of GABAA receptors regulates neuronal inhibition. PNAS. vol. 106 no. 41. 17552 –17557.
We found that blocking lysosomal degradation of GABAARs (with leupeptin treatment) or their ubiquitin-dependent lysosomal targeting (using the dominant negative GFP-2FYVE), caused a marked increase in both mIPSC amplitude and frequency suggesting not only an increase in the number of synaptic GABAARs but also an increase in the number of synaptic responses. In agreement with these findings, correlative immunofluorescence experiments revealed that blocking lysosomal GABAAR degradation resulted in an increase both in GABAAR cluster size and in the number of GABAAR clusters apposed to VIAAT positive inhibitory presynaptic terminals. The mIPSC amplitude and frequency increase is similar to that observed when surface GABAAR numbers are increased by dialysing inhibitors of GABAAR endocytosis into the postsynaptic neuron via the electrophysiological recording pipette (9). We previously suggested that this mIPSC frequency increase reflects the increase in surface GABAAR number and mIPSC amplitude unmasking mIPSCs that were previously below the threshold for detection in the recordings rather than because of a presynaptic change (9). The changes in GABAAR cluster number and mIPSC frequency that we report here are similarly likely to be because of the improved detection of existing established synapses (which before blockade of lysosomal targeting contained too few GABAARs to be detected) as a result of an increase in the availability of surface GABAARs rather than because of presynaptic effects such as increases in the probability of release.
Haspel et al. (2011) Characterization of macroautophagic flux in vivo using a leupeptin-based assay. Autophagy. 7(6):629-42
Macroautophagy is a highly conserved catabolic process that is crucial for organ homeostasis in mammals. However, methods to directly measure macroautophagic activity (or flux) in vivo are limited. In this study we developed a quantitative macroautophagic flux assay based on measuring LC3b protein turnover in vivo after administering the protease inhibitor leupeptin. Using this assay we then characterized basal macroautophagic flux in different mouse organs. We found that the rate of LC3b accumulation after leupeptin treatment was greatest in the liver and lowest in spleen. Interestingly we found that LC3a, an ATG8/LC3b homologue and the LC3b-interacting protein p62 were degraded with similar kinetics to LC3b. However, the LC3b-related proteins GABARAP and GATE-16 were not rapidly turned over in mouse liver, implying that different LC3b homologues may contribute to macroautophagy via distinct mechanisms. Nutrient starvation augmented macroautophagic flux as measured by our assay, while refeeding the animals after a period of starvation significantly suppressed flux. We also confirmed that beclin 1 heterozygous mice had reduced basal macroautophagic flux compared to wild-type littermates. These results illustrate the usefulness of our leupeptin-based assay for studying the dynamics of macroautophagy in mice. Key words: macroautophagy, autophagy, flux, mice, in vivo, LC3, GABARAP, GATE-16, leupeptin, cycloheximide.
Zhao et al. (1998) Subcellular Localization and Duration of L-Calpain and m-Calpain Activity After Traumatic Brain Injury in the Rat: A Casein Zymography Study. Journal of Cerebral Blood Flow and Metabolism 18:161-167.
Casein zymographic assays were performed to identify changes in L-calpain and m-calpain activity in naive, sham-injured, and injured rat cortex at 15 minutes, 3 hours, 6 hours, and 24 hours after unilateral cortical impact brain injury. Cortical samples ipsilateral and contralateral to the site of injury were separated into cytosolic and total membrane fractions. Marked increases in L-calpain activity in cytosolic fractions in the ipsilateral cortex occurred as early as 15 minutes, became maximal at 6 hours, and decreased at 24 hours to levels observed at 15 minutes after injury. A similar temporal profile of cytosolic L-calpain activity in the contralateral cortex was observed, although the increases in the contralateral cortex were substantially lower than those in the ipsilateral cortex. Differences were also noted between cytosolic and total membrane fractions. The detection of a shift in L-calpain activity to the total membrane fraction first occurred at 3 hours after traumatic brain injury and became maximal at 24 hours after traumatic brain injury. This shift in L-calpain activity between the two fractions could be due to the redistribution of L-calpain from the cytosol to the membrane. m-Calpain activity was detected only in cytosolic fractions. m-Calpain activity in cytosolic fractions did not differ significantly between ipsilateral and contralateral cortices, and increased in both cortices from 15 minutes to 6 hours after injury. Relative magnitudes of m-calpain versus L-calpain activity in cytosolic fractions differed at different time points after injury. These studies suggest that traumatic brain injury can activate both calpain isoforms and that calpain activity is not restricted to sites of focal contusion and cell death at the site of impact injury but may represent a more global response to injury.
Iizuka et al. (1986) Morphometric assessment of drug effects in experimental spinal cord injury. J Neurosurg 65:92-98.
The effect of large doses of methylprednisolone sodium succinate (MPSS) and two protease inhibitors, leupeptin and bestatin, on experimental acute spinal cord injury was evaluated by morphometric analysis of degenerating axons with the aid of an automated image analyzer. Spinal cord injury was produced by epidural compression with a surgical clip on the T-11 segment in rats. The extent of axonal damage was assessed in Rexed's lamina VIII in the L-6 segment by measuring the amount of silver grains, representing degenerating axons and their terminals, using the Fink-Heimer method. The severity of axonal damage was expressed as the degeneration index: that is, the amount of silver grains in experimental animals/the amount of silver grains in cord-transected animals. When examined on the 7th postoperative day, axonal degeneration in MPSS- treated rats was significantly decreased, with an average degeneration index difference of 6 (p < 0.05). Increased preservation of axons was seen in the leupeptin-treated rats sacrificed 7, 10, and 14 days after trauma. The difference in the degeneration index between the leupeptin-treated and untreated groups was 16 on Day 7 (p < 0.001), 12 on Day 10 (p < 0.001), and 13 on Day 14 (p < 0.01). Bestatin had no beneficial effect. The implications for the use of calcium-activated neutral protease inhibitors in acute spinal cord injury are discussed.
Kuiper et al. (1992) In Vivo and in Vitro Interaction of High and Low Molecular Weight Single-chain Urokinase-type Plasminogen Activator with Rat Liver Cells. J Biol Chem. Vol. 267; 3: 589-1595,
The plasma clearance and the interaction of high (HMW) and low (LMW) molecular weight single-chain urokinase-type plasminogen activator (scu-PA) with rat liver cells was determined. 1261-Labeled H MW- and LMW-scu-PA were rapidly cleared from plasma with a half-life of 0.45 min and a maximal liver uptake of 55% of the injected dose. Liver uptake of scu-PA was mediated by parenchymal cells. Excess of unlabeled HMW-scu-PA reduced the liver uptake of ‘261-HMW-scu-PA strongly. In vivo liver degradation of scu-PA was induced by inhibitors of the lysosomal pathway. A high affinity binding site (Kd45 nM, B, 1.7 pmol / mg cell protein) for both HMW- and LMW-scu-PA was determined on isolated parenchymal liver cells. Cross competition binding studies showed that LMW- and HMW-scu-PA bind to the same site. Tissue-type plasminogen activator, mannose- or galactose-terminated glycoproteins did not affect the scu-PA binding to parenchymal liver cells. It is concluded that LMW- and HMW-scu-PA are taken up in the liver by a common, newly identified recognition site on parenchymal liver cells and are subsequently degraded in lysosomes. It is suggested that this site is important for the regulation of the turnover of scu-PA.
Blisterbosch et al. (1982) Endocytosis and breakdown of mitochondrial malate dehydrogenase in the rat in vivo (Effects of suramin and leupeptin). Biochem J.; 208(1):61-7.
The plasma clearance of intravenously injected 'l25-labelled mitochondrial malate dehydrogenase (half-life 7 min) was not influenced by previous injection of suramin and/or leupeptin (inhibitors of intralysosomal proteolysis). Pretreatment with both inhibitors considerably delayed degradation of endocytosed enzyme in liver, spleen, bone marrow and kidneys. The tissue distribution of radioactivity was determined at 30min after injection, when only 3% of the dose was left in plasma. All injected radioactivity was still present in the carcass. The major part of the injected dose was found in liver (49%), spleen (5%), kidneys (13%) and bone, including marrow (11%). Liver cells were isolated 15 min after injection of labelled enzyme. We found that Kupffer cells and parenchymal cells had endocytosed the enzyme at rates corresponding to 9530 and 156 ml of plasma/day per g of cell protein respectively. Endothelial cells do not significantly contribute to uptake of the enzyme. Uptake by Kupffer cells was saturable, whereas uptake by parenchymal cells was not. This suggests that these cell types endocytose the enzyme via different receptors. Previous injection of carbon particles greatly decreased uptake of the enzyme by liver, spleen and bone marrow.
Text Selection from a Series of Related Reports (see references that follow)
Although the recovery process examined by Reddy et al. was a good model for the analysis of peroxisome degradation, they could not detect the autophagic vacuoles containing peroxisomes. The reason for the difficulty was thought to be the rapid digestion of the trapped peroxisomes in the autophagolysosomes. It was difficult to find peroxisomes trapped in autolysosomes without stopping the degradation process. For that purpose, protease inhibitors were applied to stop the degradation of sequestered materials. The exposure of isolated hepatocytes to leupeptin were known to inhibit cysteine proteases and cause a remarkable accumulation of autophagic vacuoles (28). Furthermore, intraperitoneal injection of leupeptin into rats is known to induce the accumulation of autophagic vacuoles in the hepatocytes (29). The leupeptin treatment was a useful technique, because abundant autolysosomes accumulate due to the inhibition of lysosomal degradation. Yokota studied the fate of peroxisomes by administration and withdrawal of DEHP in the presence of leupeptin followed by morphological and biochemical analyses. In the early stages of autophagosome formation, 20 min after leupeptin injection, he observed isolation membranes surrounding the target organelles (27). They were characterized by double layers with a narrow cisternal space and were negative for lysosomal membrane protein and cathepsins. In the late stages, 40–60 min after leupeptin injection, late autophagic vacuoles had single limiting membranes and were positive for lysosomal enzymes and membrane protein (30). These results suggested that newly formed autophagosomes with a double-layered membrane fused with pre-existing lysosomes and were converted into late autophagic vacuoles with a single limiting membrane. Most of the excess peroxisomes sequestered in autophagosomes were digested there by the lysosomal enzymes.
27 Yokota, S. (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by administration of dioctylphthalate. Eur. J. Cell Biol. 61, 67–80.
28. Kovacs, A. L., Reith, A., and Seglen, P. O. (1982) Accumulation of autophagosomes after inhibition of hepatocytic protein degradation by vinblastine, leupeptin or a lysosomotropic amine. Exp. Cell Res. 137, 191–201.
29. Ishikawa, T., Furuno, K., and Kato, K. (1983) Ultrastructural studies on autolysosomes in rat hepatocytes after leupeptin treatment. Exp. Cell Res. 144, 15–24.
30. Yokota, S., Himeno, M., Roth, J., Brada, D., and Kato, K. (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by di-(2-ethylhexyl)phthalate treatment. II. Immunocytochemical analysis of early and late autophagosomes. Eur. J. Cell Biol. 62, 372–383.Following
Grace Elizabeth Pluhar added an answer:Can anyone recommend a protocol for GLIOMA animal modelling ?
Has anyone tried GLIOMA animal modelling ? It will be really helpful if anyone could kindly suggest me a good protocol to follow.
Regardless of the induced model you choose, remember that there are limits to their translational relevance. Pet dogs, specifically brachycephalic breeds, develop high grade glioma spontaneously, and are a highly relevant model.Following
Maurizio Iocco added an answer:Have you ever seen in peripheral traumatic nerve injury a neurological repair without functional recovery?
I'm sure that in a few cases we have seen patient with persistent loss of function after a peripheral traumatic nerve lesion, but their conduction was normal.
Have you too?
Do you know why?
Yes I understand. It's true. But this is known for the central mechanism of recovery. but why in peripheral? I'm starting with a study about this problem.Following
Nima Derakhshan added an answer:Can glibenclamide be used as an adunctive therapy for cerebral edema in traumatic brain injury?The use of glibenclamide to control plasma glucose after TBI had no significant effect on patient outcome at discharge, but it could reduce the LOS-NICU (p<0.05). Glibenclamide also had no apparent effect on the presence of PSH in TBI patients with type 2 diabetes mellitus.Dear Kenneth
Corticosteroids are contraindicated in TBI as they resulted in worsening of outcomes in recent studies
It s a guideline according to evidence based dataFollowing
Yanick Simon asked a question:What is the reason for projectile vomiting and nausea due to elevated intracranial pressure?Elevated intracranial pressure is often associated with vomiting. I would like to know how the pressure triggers the vomiting.Following
John Daugherty added an answer:Management of post head-injury Bruxism.Patients with severe head injury esp , diffuse axonal injury may have associated bruxism which, to my experience, lasts for 10 -14 days. I have been studying these patients in recent years with trials of pramipexol and benzodiazapines. I have come across the botox inj studies as well. I wish to have suggestions from colleagues.Non-invasive treatment modalities with symptom appropriate ancillary care can be very efficacious. With any head injury the trigeminal system is ramped up and it interrupts afferent signals improperly, even normally innocuous signals. Well developed night guards can reduce the excessive motor intensity of V3 and possible on the over all upper quarter pain.
Svensson, P; Jadidi, F; Baad-Hansen, L; Sessle, B.J. Relationships between crainofacial pain and bruxism. Journal of Oral Rehabilitation, 07/2008, Volume 35, Issue 7, pp. 524 - 547.
Lobbezoo, F. Naeij, M. Bruxism is mainly regulated centrally, not peripherally. J Oral Rehabil, 2001. 28(12): p. 1085-91.Following
Mustafa Volkan YAPRAKCI added an answer:Hi everybody!This is a newly started group for everybody interested in neurotraumatology.
Closed account added an answer:Physician ScientistHallo I am new memeber of the groupWelcome!Following