Molecular Neurobiology (MOL NEUROBIOL)

Publisher: Humana Press, Humana Press

Journal description

As one of the premier review journals in the neurosciences, Molecular Neurobiology is specifically designed to synthesize and critically assess research trends in experimental and clinical neuroscience at the molecular level. Its distinguished editorial board is comprised of four Nobelists and other preeminent neuroscientists who carefully review papers to ensure their high quality.

Current impact factor: 5.14

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 5.137
2013 Impact Factor 5.286
2012 Impact Factor 5.471
2011 Impact Factor 5.735
2010 Impact Factor 6.068
2009 Impact Factor 4.735
2008 Impact Factor 3.025
2007 Impact Factor 4.067
2006 Impact Factor 3.762
2005 Impact Factor 4.311
2004 Impact Factor 4.373
2003 Impact Factor 4.516
2002 Impact Factor 2.095
2001 Impact Factor 2.4
2000 Impact Factor 4.382
1999 Impact Factor 5.623
1998 Impact Factor 4.388
1997 Impact Factor 3.483

Impact factor over time

Impact factor
Year

Additional details

5-year impact 5.46
Cited half-life 4.00
Immediacy index 1.21
Eigenfactor 0.01
Article influence 1.51
Website Molecular Neurobiology website
Other titles Molecular neurobiology
ISSN 1559-1182
OCLC 15640289
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Humana Press

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors own final version only can be archived
    • Publisher's version/PDF cannot be used
    • On author's personal website immediately
    • On any open access repository after 12 months from publication
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version: The original publication is available at www.springerlink.com
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Humana Press' is an imprint of 'Springer Verlag (Germany)'
  • Classification
    green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: Diabetes mellitus (DM) is characterized by hyperglycemia due to insulin inactivity or insufficiency with increasing risk of developing specific complications, including retinopathy, nephropathy, neuropathy, and atherosclerosis. The aim of the present study is to evaluate the efficacy of coenzyme Q10 (CoQ10), niacin, as well as their combination in ameliorating brain disorders associated with streptozotocin (STZ)-induced diabetes in rats. Glibenclamide, a reference diabetic drug, and donepezil, an acetylcholine inhibitor drug, were also evaluated. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg body weight (b.wt)). One-month diabetic rats were treated with the selected drugs daily for another two consecutive weeks. The evaluation was done through the estimation of the levels of blood glucose, serum insulin, and oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); neurotransmitters: acetylcholine (Ach) and dopamine (DA); vasoconstrictor indices: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and angiotensin II (Ang II); and apoptosis markers: tumor necrosis factor-α (TNF-α) and caspase-3 as well as the histopathological picture of the cerebellum region of the brain. The results revealed that the combination of niacin and CoQ10 improved most of the measured parameters with variable degrees. In conclusion, niacin and CoQ10 are promising dietary supplements in the management of diabetic encephalopathy.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: While many patients with hereditary optic neuropathies are caused by mitochondrial DNA (mtDNA) mutations of Leber's hereditary optic neuropathy (LHON), a significant proportion of them does not have mtDNA mutation and is caused by mutations in genes of the nuclear genome. In this study, we investigated whether the OPA1 gene, which is a pathogenic gene for autosomal dominant optic atrophy (ADOA), is frequently mutated in these patients. We sequenced all 29 exons of the OPA1 gene in 105 Han Chinese patients with suspected LHON. mtDNA copy number was quantified in blood samples from patients with and without OPA1 mutation and compared to healthy controls. In silico program-affiliated prediction, evolutionary conservation analysis, and in vitro cellular assays were performed to show the potential pathogenicity of the mutations. We identified nine OPA1 mutations in eight patients; six of them are located in exons and three are located in splicing sites. Mutation c.1172T > G has not been reported before. When we combined our data with 193 reported Han Chinese patients with optic neuropathy and compared to the available data of 4327 East Asians by the Exome Aggregation Consortium (ExAC), we found a significant enrichment of potentially pathogenic OPA1 mutations in Chinese patients. Cellular assays for OPA1 mutants c.869G > A and c.2708_2711del showed abnormalities in OPA1 isoforms, mitochondrial morphology, and cellular reactive oxygen species (ROS) level. Our results indicated that screening OPA1 mutation is needed for clinical diagnosis of patients with suspected optic neuropathy.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: Pregnancy and delivery are associated with activation of immune-inflammatory pathways which may prime parturients to develop postnatal depression. There are, however, few data on the associations between immune-inflammatory pathways and prenatal depression and physio-somatic symptoms. This study examined the associations between serum zinc, C-reactive protein (CRP), and haptoglobin at the end of term and prenatal physio-somatic symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) and prenatal and postnatal depressive and anxiety symptoms as measured using the Edinburgh Postnatal Depression Scale (EPDS), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), and Spielberger's State Anxiety Inventory (STAI). Zinc and haptoglobin were significantly lower and CRP increased at the end of term as compared with non-pregnant women. Prenatal depression was predicted by lower zinc and lifetime history of depression, anxiety, and premenstrual tension syndrome (PMS). The latter histories were also significantly and inversely related to lower zinc. The severity of prenatal EDPS, HAMD, BDI, STAI, and physio-somatic symptoms was predicted by fatigue in the first and second trimesters, a positive life history of depression, anxiety, and PMS, and lower zinc and higher CRP. Postnatal depressive symptoms are predicted by prenatal depression, physio-somatic symptoms, zinc and CRP. Prenatal depressive and physio-somatic symptoms have an immune-inflammatory pathophysiology, while postnatal depressive symptoms are highly predicted by prenatal immune activation, prenatal depression, and a lifetime history of depression and PMS. Previous episodes of depression, anxiety disorders, and PMS may prime pregnant females to develop prenatal and postnatal depressive symptoms via activated immune pathways.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disease. The major characteristics of PD include the loss of dopaminergic neurons in the substantia nigra and Lewy body depositions. Genetic defects, environment toxicants, and aging have been recognized as risk factors for the development of PD. Currently, although the pathogenesis of PD is still obscure, overwhelming evidence demonstrates that oxidative stress plays a central role in the progress of PD. Reactive oxygen species (ROS) function mainly through chemical reactions with atomic targets that lead to covalent oxidative modifications. Through the oxidative modification of ions, amino acids, amines, and nucleic acids, ROS exert augmented effects on the structures and functions of multiple macromolecules. These oxidative modifications can affect nucleic acid stability by oxidizing RNA, increasing mitochondrial DNA (mtDNA) mutation, and launching translesion synthesis (TLS); disturb protein homeostasis by accelerating α-synuclein aggregation, parkin aggregation, and proteasome dissociation; modulate dopamine release by activating ATP-sensitive potassium channels (KATP) and inactivating neuronal nicotinic acetylcholine receptors (nAChRs); and influence cellular self-defenses by promoting the cytoprotective effects of DJ-1 and PTEN-induced putative kinase 1 (PINK1) while inducing Akt dysregulation. Based on the above facts, we propose that various oxidative modifications may affect nucleic acid stability, protein homeostasis, the functionality of ion channels, and cellular self-defenses and that these processes lead to protein misfolding, dopamine depletion, and further neuronal death in PD.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg +/− ). The transgenic mice show altered level, time, and place of expression of Isl1 but are viable. However, Tg +/− mice exhibit hyperactivity, including circling behavior, and progressive age-related decline in hearing, which has been reported previously. Here, we describe the molecular and morphological changes in the cerebellum and vestibular system that may cause the hyperactivity of Tg +/− mice. The transgene altered the formation of folia in the cerebellum, the distribution of calretinin labeled unipolar brush cells, and reduced the size of the cerebellum, inferior colliculus, and saccule. Age-related progressive reduction of calbindin expression was detected in Purkinje cells in the transgenic cerebella. The hyperactivity of Tg +/− mice is reduced upon the administration of picrotoxin, a non-competitive channel blocker for the γ-aminobutyric acid (GABA) receptor chloride channels. This suggests that the overexpression of Isl1 significantly affects the functions of GABAergic neurons. We demonstrate that the overexpression of Isl1 affects the development and function of the cerebello-vestibular system, resulting in hyperactivity.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: Emerging studies suggest that endovascular treatment (EVT) may be superior to intravenous thrombolysis for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) to assess the efficacy and safety of endovascular treatment in patients with acute ischemic stroke as compared with intravenous thrombolysis. We assessed RCTs investigating EVT versus intravenous thrombolysis (IVT) published up to June 2015. In total, 21 studies of 4473 patients were included in the systematic review and meta-analysis. EVT significantly improved functional outcome at 90 days (risk ratio (RR) 1.35, 95 % confidence interval (CI) 1.18 to 1.55, I 2 = 61 %) and reduced the mortality (RR 0.81, 95 % CI 0.68 to 0.95, I 2 = 0 %), with similar symptomatic hemorrhagic transformation (SHT) rate (RR 1.12, 95 % CI 0.88 to 1.44, I 2 = 0 %). Based on the current data, endovascular therapy may produce good clinical outcomes with similar symptomatic hemorrhage and mortality as compared with intravenous thrombolysis in acute ischemic stroke. This advancing intervention is a landmark change in stroke treatment and could be of huge potential benefit to patients worldwide.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: In this study, we report the status of oxidative stress markers in vitamin B12 deficiency and their relation to clinical, laboratory, and neurophysiological findings. Fifty-one subjects with serum vitamin B12 deficiency (<211 pg/ml) were included. Plasma glutathione (GSH), malondialdehyde (MDA) and serum total antioxidant capacity (TAC) were measured in the patients and 53 controls. These markers were also compared between subacute combined degeneration (SACD) and non-SACD vitamin B12 deficiency patients groups as well as with normal controls. In the patients, GSH, MDA and TAC were correlated with demographic, clinical, hematological, biochemical, nerve conduction study (NCS), visual evoked potential (VEP) and somatosensory-evoked potential (SEP) findings. In the study group, 20 (39.2 %) patients had SACD manifesting with myeloneuropathy, cognitive or behavioral abnormalities, and 31(60.8 %) patients had non-SACD neurological manifestations. The GSH (2.46 ± 0.32 vs. 2.70 ± 0.36 mg/dl; P = 0.002) and TAC (2.13 ± 0.38 vs. 2.33 ± 0.24 nmol Trolox eq/l, P = 0.005) levels were lower, and MDA levels (4.01 ± 0.69 vs. 3.00 ± 0.45 nmol/ml, P < 0.001) were higher in B12 deficiency group compared with controls. Similar trend was found in SACD and non-SACD vitamin B12 deficiency groups. GSH levels correlated with abnormal VEP (r = 0.54; P < 0.01), TAC with female gender (r = 0.43; P = 0.002) and joint position impairment (r = -0.34; P = 0.01), and MDA with LDH (r = 0.41; P = 0.01). Vitamin B12 deficiency was associated with reduction in GSH and TAC and increase in MDA levels which were more marked in SACD compared to non-SACD group.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: Repulsive guidance molecule a (RGMa) is a membrane-bound protein that inhibits axon outgrowth in the central nervous system. Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent spontaneous seizures. To explore the role of RGMa in epilepsy, we investigated the expression of RGMa in patients with TLE, pilocarpine-induced rat model, and pentylenetetrazol kindling model of epilepsy, and then we performed behavioral, histological, and electrophysiological analysis by lentivirus-mediated overexpression of RGMa in the hippocampus of animal model. We found that RGMa was significantly decreased in TLE patients and in experimental rats from 6 h to 60 days after pilocarpine-induced seizures. In two types of epileptic animal models, pilocarpine-induced model and pentylenetetrazol kindling model, overexpression of RGMa in the hippocampus of rats exerted seizure-suppressant effects. The reduced spontaneous seizures were accompanied by attenuation of hippocampal mossy fiber sprouting. In addition, overexpression of RGMa inhibited hyperexcitability of hippocampal neurons via suppressing NMDAR-mediated currents in Mg(2+)-free-induced organotypic slice model. Collectively, these results demonstrate that overexpression of RGMa could be an alternative strategy for epilepsy therapy.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: Genetic variants found in DNA repair genes (ERCC1, rs3212986; ERCC2, rs13181; ERCC4, rs1800067; ERCC5, rs17655; XRCC1, rs1799782, rs25487, rs25489; XRCC3, rs861539) have been reported to have an ambivalent association with the development of glioma. In the present study, a meta-analysis was conducted to confirm the relationship, taking heterogeneity of population into consideration. We analyzed 21 articles of 6 genes along with 8 single nucleotide polymorphisms (SNPs) (24,078 cases and 30,926 healthy individuals), which assessed the relationship between nucleotide excision, base excision, double-strand break repair gene, and the development of glioma under five models. All statistical analysis was implemented by the software of R 3.2.1, and the relationships between key polymorphic loci in DNA repair genes and glioma were quantified by the pooled odds ratio (OR) and 95 % confidential intervals. Overall, the synthesized evidence demonstrated that the SNP of rs13181 and rs1799782 significantly increased the risk of glioma whereas SNP of rs1800067 were significantly associated with a decrease in the risk of glioma. Additionally, subgroup analyses of 8 SNPs by ethnicity indicated that the mutation of rs13181, rs1800067 were apparently protective factors of glioma among Asians, while the mutation of rs13181 was a risk factors of glioma in Caucasians. Furthermore, the mutation of rs1799782 significantly raises the risk of glioma for Asian. Our study suggested that rs13181*C and rs1799782*A are risk alleles for glioma; rs1800067*A are beneficial alleles for decreased susceptibility to glioma. Future studies with large sample size and other races are strongly recommended to confirm the results from this study.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: The tumor necrosis factor receptor-associated factors (TRAFs) have been classically described as adaptor proteins that function as solely cytosolic signaling intermediates for the TNF receptor superfamily, Toll-like receptors (TLRs), NOD, like receptors (NLRs), cytokine receptors, and others. In this study, we show for the first time that TRAFs are present within the cytoplasm and nucleus of Neuro2a cells and primary cortical neurons, and that TRAF2 and TRAF3 translocate into the nucleus within minutes of CD40L stimulation. Analysis of the transcriptional regulatory potential of TRAFs by luciferase assay revealed that each of the TRAFs differentially functions as a transcriptional activator or repressor in a cell-specific manner. Interestingly, ChIP-qPCR data demonstrate that TRAFs 2/3, p65, and pRNAPol II form part of a transcriptional complex on the Icam-1 gene promoter upon CD40L stimulation. We further determined that TRAF2 recruitment to the nucleus is critical for the ubiquitination of H2b, a transcription permissive epigenetic modification. Our findings demonstrate for the first time that TRAFs 2/3 participate in the formation of a CD40L-induced transcriptional complex in neuronal cells.
    No preview · Article · Feb 2016 · Molecular Neurobiology
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    ABSTRACT: RhoA, a member of Rho GTPases family, is known to play an important role in remodeling actin cytoskeleton. During the development of the peripheral nervous system (PNS), Schwann cells undergo proliferation, migration, and radial sorting and finally wrap the related axons compactly to form myelin sheath. All these processes involve actin cytoskeletal remodeling. However, the role of RhoA on Schwann cell during development is still unclear. To address this question, we first used a lentiviral vector-mediated short hairpin (sh) RNA targeting RhoA to knock down the expression of RhoA in the cultured Schwann cells in vitro. Effects of RhoA on Schwann cell proliferation and migration were examined by BrdU assay and transwell assay, respectively. Results of the present study indicated that downregulated RhoA expression in cultured Schwann cells significantly slacked the cells' capabilities of migration and proliferation. Then, we investigated the role of RhoA in the developing rat sciatic nerves. Immunohistology and Western blotting showed that RhoA was mainly expressed in Schwann cells in the sciatic nerves and was peaked at 2 weeks postnatal then kept in low level up to 8 weeks. In the subjected rats whose sciatic nerves were microinjected with lentiviral vectors at postnatal 3 days, we found that the lentiviruses mainly transfected Schwann cells, and the RhoA expression in the transfected Schwann cells was significantly knocked down. Four weeks after lentivirus microinjection, immunohistology and transmission electron microscopy illustrated that RhoA knockdown resulted in hypomyelination and significant decrease of the thickness of myelin in the transfected area. Overall data of current study suggested that RhoA plays a critical role in Schwann cell biology and is essential for myelination in developing peripheral nerve.
    No preview · Article · Jan 2016 · Molecular Neurobiology
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    ABSTRACT: Arachidonyl-2-chloroethylamide (ACEA), a highly selective agonist of cannabinoid receptor 1 (CB1R), has been reported to protect neurons in ischemic injury. We sought to investigate whether mitochondrial biogenesis was involved in the therapeutic effect of ACEA in cerebral ischemia. Focal cerebral ischemic injury was induced in adult male Sprague Dawley rats. Intraperitoneal injection of 1 mg/kg ACEA improved neurological behavior, reduced infarct volume, and inhibited apoptosis. The volume and numbers of mitochondria were significantly increased after ACEA administration. Expression of mitochondrial transcription factor A (Tfam), nuclear transcription factor-1 (Nrf-1), and cytochrome C oxidase subunit IV (COX IV) were also significantly up-regulated in animals administered ACEA. One thousand nanomoles of ACEA inhibited mitochondrial dysfunction in primary rat cortical neurons exposed to oxygen-glucose deprivation (OGD). Furthermore, ACEA administration increased phosphorylation of glycogen synthase kinase-3β (GSK-3β) after reperfusion. Phosphorylation of GSK-3β induced mitochondrial biogenesis and preserved mitochondrial function whereas inhibition of phosphatidylinositol 3-kinase (PI3K) dampened phosphorylation of GSK-3β and reversed induction of mitochondrial biogenesis and function following ACEA administration. In conclusion, ACEA could induce mitochondrial biogenesis and improve mitochondrial function at the beginning of cerebral ischemia, thus alleviating cerebral ischemia injury. Phosphorylation of GSK-3β might be involved in the regulation of mitochondrial biogenesis induced by ACEA.
    No preview · Article · Jan 2016 · Molecular Neurobiology
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    ABSTRACT: The aim of our study was to illuminate the potential role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder (ASD). We measured the circulating levels of BDNF in serum and BDNF gene (Val66Met) polymorphisms, in which two indicators were then compared between ASD and normal controls. A total of 82 drug-naïve ASD children and 82 age- and gender-matched normal controls were enrolled in the study. Their serum BDNF levels were detected by the ELISA. BDNF Val66Met polymorphism genotyping was conducted as according to the laboratory's standard protocol in laboratory. The ASD severity assessment was mainly determined by the score of the Childhood Autism Rating Scale (CARS). ELISA assay showed that the mean serum BDNF level of children with ASD was significantly (P < 0.0001) higher than that of the control cases (17.75 ± 5.43 vs. 11.49 ± 2.85 ng/ml; t = 9.236). Besides, the serum BDNF levels and CARS scores (P < 0.0001) were positively related. And, the BDNF genotyping results showed that there was no difference between the ASD cases and the control. Among the children with ASD, the mean serum BDNF level of Met/Met group was lower than other groups. According to the ROC curve generated from our clinical data, the optimal cutoff value of serum BDNF levels, an indicator for diagnosis of ASD, was projected to be 12.50 ng/ml. Thus, it yielded a corresponding sensitivity of 81.7 % and the specificity of 66.9 %. Accordingly, area value under the curve was 0.836 (95 % CI, 0.774-0.897); the positive predictive value (PPV) and the negative predictive value (NPV) were 70.1 and 79.1 %, respectively. These results suggested that rather than Val66Met polymorphism, BDNF was more possible to impact the pathogenesis of ASD.
    No preview · Article · Jan 2016 · Molecular Neurobiology
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    ABSTRACT: Stroke is considered as the second leading cause of death worldwide. The survivors of stroke experience different levels of impairment in brain function resulting in debilitating disabilities. Current therapies for stroke are primarily palliative and may be effective in only a small population of stroke patients. In this study, we explore the transplantation of exogenous neural stem cells (NSCs) as the potential therapy for the photothrombotic ischemia stroke in a Kunming mice model. After stroke, mice receiving NSC transplantation demonstrated a better recovery of brain function during the neurobehavioral tests. Histology analysis of the brain samples from NSC transplanted mice demonstrated a reduction of brain damage caused by stroke. Moreover, immunofluorescence assay for biomarkers in brain sections confirmed that transplanted NSCs indeed differentiated to neurons and astrocytes, consistent with the improved brain function after stroke. Taken together, our data suggested that exogenous NSC transplantation could be a promising therapy for stroke.
    No preview · Article · Jan 2016 · Molecular Neurobiology
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    ABSTRACT: In a thromboembolic stroke model after reperfusion by recombinant tissue plasminogen activator (rt-PA), we aimed to determine whether therapeutic hypothermia (TH) and ethanol (EtOH) in combination with low concentration (60 %) of normobaric oxygen (NBO) enhanced neuroprotection, as compared to using each of these agents alone. We further aimed to elucidate a potential role of the NADPH oxidase (NOX), phosphorylated protein kinase B (Akt), and protein kinase C-δ (PKC-δ) pathway in oxidative stress and neuroprotection. In Sprague-Dawley rats, a focal middle cerebral artery (MCA) occlusion was induced by an autologous embolus in the following experimental groups: rt-PA treatment alone, rt-PA + NBO treatment, rt-PA + TH at 33 °C, rt-PA + EtOH, rt-PA + NBO + EtOH, rt-PA + NBO + TH, rt-PA + NOX inhibitor, rt-PA + EtOH + NOX inhibitor, or rt-PA + EtOH + Akt inhibitor. Control groups included sham-operated without stroke or stroke without treatment. Infarct volume and neurological deficit were assessed at 24 h after rt-PA-induced reperfusion with or without treatments. ROS levels, NOX activity, and the protein expression of NOX subunits p22(phox), p47(phox), p67(phox), gp91(phox), as well as PKC-δ and phosphorylated Akt were measured at 3 and 24 h after rt-PA-induced reperfusion. Following rt-PA in thromboembolic stroke rats, NBO combined with TH or EtOH more effectively decreased infarct volume and neurological deficit, as well as reactive oxygen species (ROS) production than with any of the used monotherapies. NOX activity and subunit expressions were downregulated and temporally associated with reduced PKC-δ and increased p-Akt expression. The present study demonstrated that combining NBO with either TH or EtOH conferred similar neuroprotection via modulation of NOX activation. The results suggest a role of Akt in NOX activation and implicate an upstream PKC-δ pathway in the Akt regulation of NOX. It is possible to substitute EtOH for TH, thus circumventing the difficulties in clinical application of TH through the comparatively easier usage of EtOH as a potential stroke management.
    No preview · Article · Jan 2016 · Molecular Neurobiology
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    ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR) is key enzyme of folate/homocysteine pathway. Case control association studies on MTHFR C677T polymorphism and Alzheimer's disease (AD) have been repeatedly performed over the last two decades, but the results are inconclusive. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for AD. Forty-one studies were identified by a search of PubMed, Google Scholar, Elsevier, and Springer Link databases, up to January 2015. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effect model or random effect model. The subgroup analyses based on ethnicity were performed. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C OR = 1.29, 95 % CI = 1.07-1.56, p = 0.003; for TT + CT vs CC OR = 1.29, 95 % CI = 1.19-1.40, p = 0.0004; for TT vs CC OR = 1.31, 95 % CI = 1.16-1.48, p = 0.001; for CT vs CC OR = 1.24, 95 % CI = 1.13-1.35, p < 0.004; and for TT vs CT + CC OR = 1.13, 95 % CI = 1.00-1.28, p = 0.02). Results of present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD.
    No preview · Article · Jan 2016 · Molecular Neurobiology