Exercise test for patients with new-onset paroxysmal kinesigenic dyskinesia.

The pathogenesis of primary paroxysmal kinesigenic dyskinesia (PKD) remains unclear, and channelopathy is a possibility. In a pilot study, we found that PKD patients had abnormal exercise test (ET) results. To investigate the ET performances in patients affected by PKD, and the role of the channelopathies in the pathogenesis of PKD, we compared the ET results of PKD patients, control subjects, and hypokalemic periodic paralysis (HoPP) patients, and we analyzed ET changes in 32 PKD patients before and after treatment. Forty-four PKD patients underwent genetic testing for the PRRT2, SCN4A, and CLCN1 genes. Sixteen of 59 (27%) patients had abnormal ET results in the PKD group, while 28 of 35 (80%) patients had abnormal ET results in the HoPP group. Compared with the control group, the PKD group showed a significant decrease in the compound muscle action potential (CMAP) amplitude and area after the long ET (LET), while the HoPP group showed not only greater decreases in the CMAP amplitude and area after the LET but also greater increases in the CMAP amplitude and area immediately after the LET. The ET parameters before and after treatment were not significantly different. Nine of 44 PKD patients carried PRRT2 mutations, but the gene abnormalities were unrelated to any ET parameter. The PKD group demonstrated an abnormal LET result by electromyography (EMG), and this abnormality did not seem to correlate with the PRRT2 variant or sodium channel blocker therapy.

Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting ß-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aß formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aß formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.-Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

Correlation of Stress Hyperglycemia after Ischemic Stroke with Early Vascular Cognitive Impairment.

Objective To investigate the influence and forecast value of stress hyperglycemia on the early vascular cognitive impairment (VCI) in stroke patients.Methods Totally 422 patients with acute non-diabetic stroke were divided into three groups according to the fasting plasma glucose level:the euglycemia group (<6.1 mmol/L),the mild stress hyperglycemia group (6.1-7.0 mmol/L),and the severe stress hyperglycemia group (≥7.0 mmol/L).Mini-mental state examination,Alzheimer's disease rating scale cognitive subscale,and clinical dementia rating scale were used to evaluate early cognition in post-stroke patients,and patients were divided into three groups accordingly:normal cognitive function group,mild VCI group,and vascular dementia group.Correlation analysis was carried out on the level of stress hyperglycemia and the degree of VCI.Results Of these 422 patients,stress hyperglycemia was identified in 62 cases (14.7%).The risk of stress hyperglycemia was higher in patients with a high degree of education [(8.39±3.85)years vs.(6.62±4.39)years,P=0.037)] or a history of cardiovascular disease (45.2% vs.18.3%,P=0.001).VCI was detected in 270 patients (64.0%).Age,sex,smoking,National Institute of Health Stroke Scale score,Hamilton Depression Rating Scale score,stress hyperglycemia,and history of cardiovascular disease were related with early VCI after non-diabetic ischemic stroke (P<0.05).Multivariate Logistic regression analysis showed that stress hyperglycemia was an independent risk factor for VCI in patients with non-diabetic ischemic stroke (OR=3.086,95% CI=1.065-8.929).The risks of cognitive impairment in the mild stress hyperglycemia group and the severe stress hyperglycemia group were higher than that of the euglycemia group,while it was also higher in the severe stress hyperglycemia group than in the mild stress hyperglycemia group (61.11% vs.75.00% vs.90.91%).Stress hyperglycemia was positively correlated with the high risk of early cognitive impairment in stroke patients (rs=0.185,P=0.007).Conclusion There is a significant correlation between stress hyperglycemia and early VCI after ischemic stroke.

[Carotid artery dissection with Horner syndrome as main manifestation: a case report].

A 44-year old male patient was admitted to the First Affiliated Hospital, Zhejiang University School of Medicine with left ptosis and pain on the left head and neck for 20 days.Brain MRI showed subacute cerebral infarction on left parietal lobe and intramural hematoma on left internal carotid artery. CT angiography showed stenosis line on the C1 segment of left internal carotid artery. Digital subtraction angiography showed dissection on the C1 segment of left internal carotid artery.The condition of patients was improved after anticoagulant therapy.

Factors of Hamilton Depression Rating Scale (17 items) at 2 weeks correlated with poor outcome at 1 year in patients with ischemic stroke.

There was fewer paper about the relation between the Hamilton Depression Rating Scale (17 Items, HDRS-17) factors and stroke outcomes. Our aim was to investigate the influence of total score and factors of HDRS-17 on outcome of ischemic stroke at 1 year. A total of 1,953 patients with acute ischemic stroke were enrolled into a multicentered and prospective cohort study. The HDRS-17 was used to assess symptoms at 2 weeks after ischemic stroke. The Modified Ranking Scale (mRS) scores of 3-6 points and 0-2 points were regarded as poor outcome and benign outcome, respectively. At 1 year, 1,753 (89.8 %) patients had mRS score data. After adjusting for the confounders, patients with a total HDRS-17 score of ≥ 8 had a worse outcome at 1 year (OR = 1.62, 95 % CI 1.18-2.23). Symptoms of suicide (OR = 1.89, 95 % CI 1.27-2.83), decreased or loss of interest of work (OR = 1.89, 95 % CI 1.38-2.58), retardation (OR = 1.74, 95 % CI 1.27-2.38), psychic anxiety (OR = 1.72, 95 % CI 1.26-2.34), and agitation (OR = 1.61, 95 % CI 1.08-2.40) increased the risks for poor outcome by >60 %, respectively. Depressed mood, somatic anxiety, somatic symptoms-gastrointestinal, and early insomnia also increased the risk for poor outcome by nearly 50 %, respectively. A total HDRS-17 score of ≥ 8, and suicide, decreased or loss of interest of work, anxiety, agitation, retardation, depressed mood, somatic anxiety, somatic symptoms-gastrointestinal, and early insomnia of the HDRS-17 factors at 2 weeks after ischemic stroke increase the risk for poor outcome at 1 year.

Meningoencephalitis as an initial manifestation of neuromyelitis optica spectrum disorder.

Two patients presented with initial symptoms of headache and fever, and two weeks later had disturbance of consciousness. Cerebrospinal fluid (CSF) showed pleocytosis >500×10²/L. Magnetic resonance imaging (MRI) showed multiple brain lesions at sites of high aquaporin-4 (AQP-4) expression. Case 1 presented optic neuritis four years after the first attack and case 2 had symptoms of myelitis three weeks after headache. Serum AQP-4 antibody was positive in both cases, and the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) was made. Accordingly, NMOSD can initially present as meningoencephalitis mimicking intracranial infection, and the characteristic MRI imaging is quite critical for differentiation.

[The association between plasma neurotransmitters levels and depression in acute hemorrhagic stroke].

OBJECTIVE: To explore the relation between plasma neurotransmitters (Glutamic acid, GAA; γ-aminobutyric acid, GABA; 5-hydroxytryptamine, 5-HT; and noradrenaline, NE) and depression in acute hemorrhagic stroke. METHODS: Objectives were screened from consecutive hospitalized patients with acute stroke. Fasting blood samples were taken on the day next to hospital admission, and neurotransmitters were examined by the liquid chromatography-high resolution mass spectrometry (LC-HRMS). The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) was used to diagnose depression at two weeks after onset of stroke. The modified Ranking Scale (mRS) was followed up at 1 year. Pearson test was used to analyse the correlation between serum concentration of neurotransmitters and the Hamilton Depression scale-17-items (HAMD-17) score. Logistic regression was used to analyse the relation of serum concentration of neurotransmitters and depression and outcome of stroke. RESULTS: One hundred and eighty-one patients were included in this study. GABA significantly decreased [6.1(5.0-8.2) µg/L vs 8.1(6.3-14.7) µg/L, P < 0.05] in patients with depression in hemorrhagic stroke, and there was no significant difference in GAA, 5-HT, or NE. GABA concentration was negatively correlated with HAMD-17 score (r = -0.131, P < 0.05); while concentration of serum GABA rose by 1 µg/L, risk of depression in acute phase of hemorrhagic stroke was reduced by 5.6% (OR 0.944, 95%CI 0.893-0.997). While concentration of serum GAA rose by 1 µg/L, risk of worse outcome at 1 year was raised by 0.1%, although a statistic level was on marginal status (OR 1.001, 95%CI 1.000-1.002). CONCLUSIONS: In patients with depression in the acute phase of hemorrhagic stroke, there was a significant reduction in plasma GABA concentration. GABA may have a protective effect on depression in acute phase of hemorrhagic stroke. Increased concentrations of serum GAA may increase the risk of worse outcomes at 1 year after stroke.

The role of purinergic receptors in neural repair and regeneration after spinal cord injury.

Spinal cord injury is a serious injury of the central nervous system that results in neurological deficits. The pathophysiological mechanisms underlying spinal cord injury, as well as the mechanisms involved in neural repair and regeneration, are highly complex. Although there have been many studies on these mechanisms, there is no effective intervention for such injury. In spinal cord injury, neural repair and regeneration is an important part of improving neurological function after injury, although the low regenerative ability of nerve cells and the difficulty in axonal and myelin regeneration after spinal cord injury hamper functional recovery. Large amounts of ATP and its metabolites are released after spinal cord injury and participate in various aspects of functional regulation by acting on purinergic receptors which are widely expressed in the spinal cord. These processes mediate intracellular and extracellular signalling pathways to improve neural repair and regeneration after spinal cord injury. This article reviews research on the mechanistic roles of purinergic receptors in spinal cord injury, highlighting the potential role of purinergic receptors as interventional targets for neural repair and regeneration after spinal cord injury.

Cytokine gene polymorphisms and Parkinson's disease: a meta-analysis.

BACKGROUND: Cytokines, which are involved in immunological responses, play and important role in the development and progression of Parkinson's disease (PD). The functional polymorphisms identified in cytokine genes are thought to influence PD risk. However the findings of studies investigating the association between cytokine gene polymorphisms and PD risk are still controversial. Therefore, we conducted a meta-analysis, in order to investigate the potential associations between cytokine gene polymorphisms and PD. METHODS: Studies of PD and cytokine polymorphisms were identified by searches of PubMed and PDGene. Pooled analyses were performed to assess the association between cytokine gene polymorphisms and PD. RESULTS: Our results indicated a positive association of TNFα -1031 CC genotype in overall analysis(CC vs. TT: OR=3.146; 95%CI: 1.631-6.070, p=0.008; CC vs. CT+TT: OR=3.187: 95%CI: 1.657-6.128,p=0.008), and an Asian subgroup, C variant(OR=1.328; 95%CI: 1.053-1.675, p=0.034) also conveyed an increased PD risk as well as CC genotype ( CC vs. TT: OR=3.207; 95%CI: 1.614-6.373, p=0.004; CC vs. CT+TT: OR=3.238; 95%CI: 1.636-6.410, p=0.004). A decreased risk for PD was associated with IL-6-174C allele (OR=0.761; 95%CI: 0.641-0.903, p=0.008) and IL-1RA VNTR 2 allele(OR=0.641; 95%CI: 0.456-0.826 p=0.004). For the polymorphisms of IL-1ß C[-511]T, IL-1α C[-889]T , TNFα G[-308]A, and IL-10 G[-1082]A no significant association was found between the gene polymorphisms and PD risk. CONCLUSIONS: Our meta-analysis suggested that gene polymorphisms of TNFα -1031, IL-6-174 and IL-1RA VNTR may be associated with PD risk. However, more large well-designed studies will be necessary to validate our findings.

Repetitive transcranial magnetic stimulation in combination with citalopram in young patients with first-episode major depressive disorder: a double-blind, randomized, sham-controlled trial.

OBJECTIVES: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) started with citalopram in first-episode young major depressive patients. METHODS: In a 2-week double-blind study with a 2-week extended antidepressant phase, 60 first-episode young major depressive patients were randomly assigned to citalopram in combination with 2 weeks of either active or sham rTMS treatment. During the following 2 weeks, the patients continued only the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17) and Montgomery-Asberg depression rating scale (MADRS) were used to assess the severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail-Making Test (TMT), and Stroop Color-Word Test (SCWT) were used to assess executive function. RESULTS: (1) There was a significantly greater number of early improvers (a reduction of HAMD-17 score ≥ 20% within the first 2 weeks) observed in the active rTMS group compared to the sham group (57% vs. 29%, χ(2)=4.667, p=0.031). (2) There was no significant difference observed in responder rates (46% vs. 36%, χ(2)=0.295, p=0.586) or in remission rates (39% vs. 29%, χ(2)=0.319, p=0.572) between the two groups at 4 weeks. (3) There was a significant difference seen in both HAMD-17 and MADRS scores between the two groups at 2 and 4 weeks. The active rTMS group showed a significantly faster score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444, p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients did not deteriorate in executive performance, and even improved in categories on WCST and completed TMT faster in the active group. CONCLUSIONS: RTMS accelerated the rapidity of the antidepressant response in first-episode young depressive patients. Our results call for future rTMS studies with larger sample sizes, high intensity of stimuli, and longer duration to draw more definitive conclusions.

The relationship between a fish-rich diet and poststroke cognitive impairment: A cross-sectional study with a follow-up in China.

ABSTRACT: Whether a fish-rich diet is positively associated with cognitive function after stroke remains unclear; thus, the present study investigated the relationship between them.The present study was part of a prospective multicenter study, in which 920 individuals (609 males, mean age, 62.78 ±â€Š11.79 years) were included from November 2013 to December 2015. The cognitive function of the patients was evaluated, and the diagnosis of poststroke cognitive impairment (PSCI) was made during their stay in the hospital. A subgroup of 439 patients from a single center was followed up for 4 to 6 years and was reassessed for cognitive function.According to the diagnostic criteria, the PSCI prevalence was lower in the fish-rich diet group (P < .05). After adjusting for demographic and clinical variables by logistic regression, patients with a habit of consuming a fish-rich diet had a lower risk of developing PSCI than patients without a fish-rich diet (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.46-0.95). When MMSE score was considered the cognitive function outcome variable, the long-term cognitive function of the fish-rich diet group was better (28 [26-30] vs 27 [25-29], P < .01), but the statistical results were not significant after correcting for the related confounding factors (ß: 0.13; 95% CI: -0.99-1.25; P = .82).There was a negative relationship between consuming a fish-rich diet and the prevalence of PSCI, and there was no statistically significant difference in the relationship of a fish-rich diet on long-term cognitive function after stroke, which requires further study.

Temporal coincidence of myasthenia gravis and Guillain Barré syndrome associated with Hashimoto thyroiditis.

Both myasthenia gravis (MG) and Guillain Barré syndrome (GBS) are autoimmune diseases leading to muscle weakness, while the temporal coincidence of MG and GBS is rare. Here, we report a case of MG and GBS, as well as Hashimoto's thyroiditis, for the first time. All these diseases were relieved by immunomodulatory therapy, which suggested abnormal regulation of the autoimmune system might be the cause in our case. In addition, MG was not diagnosed at first from the initial symptom of unilateral lateral rectus muscle palsy.

[Repetitive transcranial magnetic stimulation combined with antidepressant medication in treatment of first-episode patients with major depression].

OBJECTIVE: To assess the early therapeutic and cognitive effect of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressant medication in treatment of first-episode patients with major depression. METHODS: Sixty first-episode depressed inpatients aged 18-45 y, who met the DSM-IV clinical criteria for major depressive episode were randomly assigned to citalopram treatment (20 mg/d) in combination with a two-week period of either rTMS (study group)or sham procedure (control group) on left dorsal-lateral prefrontal cortex (10 Hz, 90% motor threshold). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of depression. The Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) were used to assess cognitive function of depression. RESULT: The response rate was significantly greater in the study group compared to the control group after treatment (57% compared with 29%,P<0.05). The HAMD scores significantly declined after treatment in two groups, and the study group showed lower scores compared to the control group after 2 weeks (P<0.01). Neuropsychological assessments showed that there was no significant difference between the two groups except for the significant improvement in the categories on WCST in study group compared to the baseline (P<0.05) and the control group (P<0.05)after 2 weeks treatment. No serious event occurred in the patients during the rTMS study. CONCLUSION: 10 Hz rTMS enhances early effects of citalopram and improves cognitive function in first-episode major depressive patients.

Neuromodulatory therapies for patients with prolonged disorders of consciousness.

BACKGROUND: Reviving patients with prolonged disorders of consciousness (DOCs) has always been focused and challenging in medical research. Owing to the limited effectiveness of available medicine, recent research has increasingly turned towards neuromodulatory therapies, involving the stimulation of neural circuits. We summarised the progression of research regarding neuromodulatory therapies in the field of DOCs, compared the differences among different studies, in an attempt to explore optimal stimulation patterns and parameters, and analyzed the major limitations of the relevant studies to facilitate future research. METHODS: We performed a search in the PubMed database, using the concepts of DOCs and neuromodulation. Inclusion criteria were: articles in English, published after 2002, and reporting clinical trials of neuromodulatory therapies in human patients with DOCs. RESULTS: Overall, 187 published articles met the search criteria, and 60 articles met the inclusion criteria. There are differences among these studies regarding the clinical efficacies of neurostimulation techniques for patients with DOCs, and large-sample studies are still lacking. CONCLUSIONS: Neuromodulatory techniques were used as trial therapies for DOCs wherein their curative effects were controversial. The difficulties in detecting residual consciousness, the confounding effect between the natural course of the disease and therapeutic effect, and the heterogeneity across patients are the major limitations. Large-sample, well-designed studies, and innovations for both treatment and assessment are anticipated in future research.

Novel compound heterozygous of PARKIN causes early-onset Parkinson's disease.

Genetics has an essential role in the development of early-onset Parkinson's disease (EOPD). Consequently, genetic screening is of great significance for the diagnosis and treatment of EOPD. In this study, we reported two EOPD with compound heterozygous in PARKIN detected by whole-exome sequencing (WES) and ligation-dependent probe amplification (MLPA). Two unrelated EOPD patients and their parents were enrolled in this study. Genetic analysis was performed through WES and verified by direct Sanger sequencing. In addition, MLPA was used to detect exon dosage. Detailed clinical manifestations and several scale assessments were collected for genotype and phenotype analysis. Compound heterozygous mutations in PARKIN were identified in both patients. c.735-1G > A and Ex2del were detected in Case A, while G284R (c.850 G > C) and Ex2del were found in Case B. These variants were confirmed to originate from their normal parents. The c.735-1G > A is a novel PARKIN variant, which was predicted to result from disappearing of the acceptor splice site by NetGene2. The G284R is a previously reported pathological mutation and the Ex2del is a hot variant of PARKIN found in the Asian population. The phenotypes of both patients are quite different, the main manifestation of case A is rigidity onset, while the case B starts with tremor and foot dystonia. In the present study, we reported a novel compound heterozygous form of PARKIN consisting of splice variant c. 735-1G > A and Ex2del. Moreover, we also found that tiny differences in genotypes of PARKIN may lead to obvious clinical phenotypic differences.

Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study).

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

[Interaction of microRNA-338 and its potential targeting protein eiF4E3].

OBJECTIVE: To analyze the interaction between the microRNA-338 and its targeting proteins during the cerebral ischemia and reperfusion injury. METHODS: TargetScan was used to predict the targets of microRNA-338. The potential targeting proteins were then selected according to their secondary structures using RNA structure 4.6 software and their involvement in cerebral ischemia and reperfusion injury was studied. Dual-luciferase reporter assay was used to testify whether microRNA-338 can recognize the 3'UTR of target protein. Western blot was applied to analyze the expression of eiF4E3 in both experimental group and control group. RESULT: EiF4E3 was the most likely potential targeting protein of microRNA-338. The secondary structure of local region of eiF4E3 recognizing microRNA-338 was conservative. The ratio of firefly to renilla luciferase activity in the experimental group was much higher than that of control group. However, there was no significant difference in the expression of eiF4E3 between these two groups. CONCLUSION: MicroRNA-338 can recognize the 3'UTR of eiF4E3 while it has no significant effect on the expression of eiF4E3. The post-target-recognizing regulation for miRNA do exist and this mechanism is possibly related to the tertiary structure of target mRNA.

[The properties and research methods of pannexins].

The gene encoding pannexin is a new gap junction family member discovered in 2000. Recent studies indicated that pannexin protein can form hemichannel on the membrane or intercellular gap junction channel, which is involved in many physiological and pathological activities. Here, we make a review of the latest research progress on the expression and cellular localization, the channel properties and the research methods of pannexins in an attempt to provide some evidences and methodological references to further investigation on the physiological and pathological functions of pannexin.

Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination.

Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is downregulated by PDGF stimulation and upregulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3ß and regulated its activity, and thereby affects the nuclear accumulation of ß-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.

The bradykinin B2 receptor mediates hypoxia/reoxygenation induced neuronal cell apoptosis through the ERK1/2 pathway.

The bradykinin B2 receptor (B2R) mediates many physiological processes such as hypotension, inflammation and blood-vessel permeability. Hypoxia/reoxygenation (H/R) induces neuronal cell apoptosis. It was found that B2R expression was enhanced in primary cultured cortical neurons after H/R treatment. Addition of bradykinin (BK) alleviated the neuronal damage from H/R. This protective effect of BK was inhibited by the B2R antagonist, HOE140, and the ERK1/2 antagonist, PD98059. The phosphorylation of ERK1/2 was increased under H/R, and the addition of BK enhanced this effect. These results indicate that B2R plays an important role in protecting neurons from damage induced by H/R and this effect may function through the ERK1/2 pathway.