The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA

Objectives: To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA.

Methods: From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events.

Results: We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77–11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41–7.91, p = 0.006) was independently associated with recurrent ischemic events.

Discussion: In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.     

Geranylgeranylacetone exerts neuroprotective roles through medicating the phosphatidylinositol-3 kinase/Akt signaling pathway in an intracerebral hemorrhage rat model

Aim: Previous studies have demonstrated that geranylgeranylacetone exerts neuroprotective effects in experimental intracerebral hemorrhage. This study is designed to explore the underlying mechanism.

Materials and Methods: One hundred and eighty male Sprague–Dawley rats were subjected to intracerebral hemorrhage by stereotactic injection of collagenase and were pretreated without or with different doses of geranylgeranylacetone. At 6 h, 24 h, 48 h, 72 h and 7 days after the operation, the neurological deficits were examined with the scoring scale method. To explore the underlying mechanism, wortmannin (Wort), a specific phosphatidylinositol-3 kinase (PI3K) inhibitor, was used. The protein expression of Akt was determined by Western blotting. The brain water content and the hematoma volume assessment were measured and compared among the different groups.

Results: We first found that geranylgeranylacetone pretreatment significantly reduced neurological deficit in intracerebral hemorrhage rats, indicating its neuroprotective role. Then, we found wort treatment significantly decreased the geranylgeranylacetone-induced Akt expression level in intracerebral hemorrhage rats. Besides, wort not only reversed the effects of geranylgeranylacetone on neurological function, but also reversed the effects of geranylgeranylacetone on reducing brain edema and decreasing hematoma volume in intracerebral hemorrhage rats.

Conclusion: Geranylgeranylacetone exerts neuroprotective roles, at least partially, through medicating the PI3K/Akt signaling pathway in an experimental intracerebral hemorrhage rat model.     

Effects of constraint-induced movement therapy on brain glucose metabolism in a rat model of cerebral ischemia: a micro PET/CT study

Purpose: Constraint-induced movement therapy (CIMT) can improve motor functions in stroke patients and ischemic rats. This study examined the effect of CIMT in ischemic rats using positron emission tomography (PET).

Methods: We used middle cerebral artery occlusion (MCAO) procedure to induce cerebral ischemia in rats. Male rats were divided into a negative control group (Normal, n = 4), a sham-operated group (Sham, n = 6), an ischemic group (Control, n = 6) and an ischemic CIMT-treated group (CIMT, n = 6). CIMT started at postoperative day 8 (d8) and lasted for 2 weeks. We utilized 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) micro PET/CT imaging to evaluate glucose metabolism in different brain regions at baseline, before, and after treatment, respectively.

Results: CIMT improved behavioral performance in the ischemic CIMT group. At the end of treatment, the CIMT group showed lower standardized uptake values (SUVs) in the ipsilateral cingulate, motor and somatosensory cortex, respectively; as well as the anterodorsal hippocampus compared to the Control group (1.80% ± 0.10% vs. 1.92% ± 0.08%, 1.32% ± 0.14% vs. 1.48% ± 0.09%, 1.18% ± 0.14% vs. 1.42% ± 0.15%, 1.68% ± 0.09% vs. 1.79% ± 0.06%, P < 0.05). We also observed higher SUVs in the acbcore shell and cortex insular of the contralateral hemisphere compared to the Control group (2.07% group in the acbcore shell and cortex insular of contralateral P < 0.05).

Conclusion: CIMT improved behavioral outcomes in cerebral ischemic rats and this effect can be attributed to increased glucose utilization in the contralateral hemisphere.     

Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke

Objective: Neuroserpin (NSP) is known for its neuroprotective effects. The aim of this study was to investigate the relationship between NSP level and clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke.

Methods: A total of 133 patients with acute cerebral infarction (ischemia group) and 44 controls were recruited. The modified Rankin Scale (mRS) was used to determine the functional outcome three months after onset. We investigated the relationship between serum NSP levels [on admission and a decrease in NSP levels (10 days after admission versus on admission)] and serum levels of several inflammatory markers.

Results: We confirmed that NSP levels on admission in the ischemia group were significantly higher than those in the control group. NSP levels in patients with good outcomes were significantly higher than those in patients with poor outcomes. NSP levels on admission were associated with having a good outcome in these patients. We found that a larger decrease in NSP levels (on admission vs. 10 days after admission) was correlated with lower serum levels of IL-6, IL-1β, and ICAM-1 10 days after admission.

Conclusions: A larger decrease in NSP levels related to lower levels of inflammatory marker, while higher NSP levels were associated with lower inflammatory markers and better functional outcomes. Decreasing the infarct size may play a role in this process. These results provide more evidence of the neuroprotective effect of NSP in cerebral ischemic patients. Decrease in the Serum NSP level and NSP level at admission may be considered as potential predictive factors for outcome of acute ischemic stroke.     

Promoting physical activity in hospitalized patients with mild ischemic stroke: a pilot study

Background: Patients with acute stroke spend most of their hospital day inactive. However, a method to promote physical activity (PA) in stroke has not been established.

Objective: To evaluate the effectiveness of promoting PA by enhancing self-efficacy in hospitalized patients with mild ischemic stroke.

Design: Pre–post interventional study.

Methods: Hospitalized patients with mild ischemic stroke who could walk without assistance were recruited. We measured the daily number of steps taken as the index of daily hospitalized PA using an accelerometer. At the baseline measurement, patients did not receive accelerometer-based feedback. To promote hospitalized PA, a physical therapist provided instruction on the self-monitoring approach and discussed PA targets, encouraged the patients to walk more, and instructed them on the importance of PA after stroke. We also measured self-efficacy for PA using an assessment tool at the baseline and during the intervention.

Results: Twenty-two patients (62.5 years old, 68.2% men) were included. PA during the intervention was higher than that at the baseline measurement (5709.4 ± 2236.1 vs. 2813.9 ± 1511.9 steps/day, p < 0.001). Self-efficacy for PA during the intervention was also higher than that at the baseline measurement (76.4 ± 18.8 vs. 58.9 ± 29.0 points, p < 0.001).

Conclusions: Promoting PA by enhancing self-efficacy may increase PA and self-efficacy for PA in hospitalized patients with mild ischemic stroke. The present results might provide new strategies of PA promotion in these hospitalized patients.     

Post-stroke hemiparesis: Does chronicity,etiology, and lesion side are associated with gait pattern?

Background: Studies that evaluate gait rehabilitation programs for individuals with stroke often consider time since stroke of more than six months. In addition, most of these studies do not use lesion etiology or affected cerebral hemisphere as study factors. However, it is unknown whether these factors are associated with post-stroke motor performance after the spontaneous recovery period.

Objective: To investigate whether time since stroke onset, etiology, and lesion side is associated with spatiotemporal and angular gait parameters of individuals with chronic stroke.

Methods: Fifty individuals with chronic hemiparesis (20 women) were evaluated. The sample was stratified according to time since stroke (between 6 and 12 months, between 13 and 36 months, and over 36 months), affected cerebral hemisphere (left or right) and lesion etiology (ischemic and hemorrhagic). The participants were evaluated during overground walking at self-selected gait speed, and spatiotemporal and angular gait parameters were calculated.

Results Differences between gait speed, stride length, hip flexion, and knee flexion were observed in subgroups stratified based on lesion etiology. Survivors of a hemorrhagic stroke exhibited more severe gait impairment. Subgroups stratified based on time since stroke only showed intergroup differences for stride length, and subgroups stratified based on affected cerebral hemisphere displayed between-group differences for swing time symmetry ratio.

Conclusion: In order to recruit a more homogeneous sample, more accurate results were obtained and an appropriate rehabilitation program was offered, researchers and clinicians should consider that gait pattern might be associated with time since stroke, affected cerebral hemisphere and lesion etiology.     

MiR-125b blocks Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rat models of cerebral ischemia-reperfusion injury by targeting p53

Objective: To explore the potential effect of miR-125b on p53-mediated regulation of Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rats with cerebral ischemia-reperfusion (CIR) injury.

Methods: Sprague-Dawley (SD) rats were used to conduct CIR injury and injected with miR-125b mimic/inhibitor or p53 inhibitor (Pifithrin-α, PFT-α). Dual-luciferase reporter gene assay was used to analyze the targeting relationship between miR-125b and p53. Longa scoring and Triphenyl tetrazolinm chloride (TTC) staining were used to test the neurologic function and determine infarct size, respectively. Hematoxylin-eosin (HE) and Nissl’s stainings were conducted to observe the morphology of cortical neurons. Neuronal nuclei (NeuN) expression was detected by immunohistochemical staining. QRT-PCR was performed to detect the expressions of miR-125b and p53. TUNEL staining and Western blotting was used to determine neuronal apoptosis and expressions of Bax/Cytochrome C/Caspase-3 signaling pathway-related proteins, respectively.

Results: Our results showed that miR-125b could directly target p53. As observed, overexpression of miR-125b could obviously reduce the neurological score, infarct size, and brain water content after CIR in rats, which also improved the morphology of cortical neurons, increased the number of neurons, reduced neuronal apoptosis, and inhibited the expressions of Bax/Cytochrome C/Caspase-3 pathway. Moreover,the similar results were observed in rats with CIR after injected with PFT-α. But no significant differences in each index were found in CIR group and CIR + anti-miR-125b + PFT-α group.

Conclusion: MiR-125b exerts protective effects on CIR injury through inhibition of Bax/Cytochrome C/Caspase-3signaling pathway via targeting p53, which is likely to be a promising treatment for CIR.

Abbreviations: 3’–UTR: 3–untranslated region; CIR: cerebral ischemia–reperfusion; CIS: cerebral ischemic stroke; PFT–α: Pifithrin–α; PVDF: polyvinylidene fluoride; SD: Sprague–Dawley; TBST: tris buffered saline with tween. TTC staining: Triphenyl tetrazolinm chloride staining; TUNEL: Terminal deoxynucleotidyl transferase–mediated dUTP–biotin nick end labeling.     

Atherosclerotic plaque burden of middle cerebral artery and extracranial carotid artery characterized by MRI in patients with acute ischemic stroke in China: association and clinical relevance

Objectives: This study sought to compare the atherosclerotic plaque burden between middle cerebral artery (MCA) and extracranial carotid artery (ECA) in ischemic stroke patients using high-resolution, black-blood (HR BB) MRI and to investigate the relationship between plaque burden found in both arteries and stroke severity.

Methods: All subjects with recent ischemic stroke underwent MCA and ECA HR BB MRI at 3.0 Tesla. For each artery segment, the thickness, area and signal intensities of plaques were recorded. Plaque burden, as measured by normalized wall index (NWI = wall area/total vessel area × 100%) were calculated. All patients received a clinical stroke severity score as measured by the National Institutes of Health Stroke Scale (NIHSS) scores at the time of admission.

Results: A total of 65 stroke subjects were included in the final analysis. MCA exhibited significantly greater NWI than the ipsilateral ECA (symptomatic MCA vs. ECA: 58.04 ± 8.19 vs. 37.53 ± 10.25, p < 0.001; asymptomatic MCA vs. ECA: 53.80 ± 4.49 vs. 34.85 ± 4.27, p < 0.001, respectively). NWI in symptomatic MCA and ECA were significantly associated with NIHSS scores (r = 0.779 vs. 0.645; p < 0.001 respectively). Moreover, stronger statistical correlations between NIHSS scores and NWI were found in MCA, as compared with ECA during multivariate linear regression analysis.

Conclusion: Greater atherosclerotic plaque burden and a closer association with stroke severity were found for the MCA as compared to the ipsilateral ECA. Identification of MCA plaque lesions by MRI may be helpful for developing more aggressive strategies for stroke prevention.     

Neuroprotective effect of G14-humanin on global cerebral ischemia/reperfusion by activation of SOCS3 – STAT3 – MCL–1 signal transduction pathway in rats

Objective: Humanin (HN) has been identified to suppress neuron death. Gly¹⁴-HN (HNG), as a variant of HN, can decrease infarct volume after ischemia/reperfusion (I/R) injury. This study aimed to investigate the neuroprotective mechanism of HNG on global cerebral I/R (GI) in rats.

Methods: Rats were randomly divided into 13 groups: Sham group, GI groups and HNG groups. Both GI group and HNG groups included six time points (1, 3, 6, 12, 24, and 72 h). At 24 h after reperfusion, Nissl staining was used to observe positive neurons, and p-STAT3, MCL-1, SOCS3, Bax and Caspase-3 in different groups were detected by immunohistochemistry. qRT-PCR and western blot were used to evaluate the expression of STAT3, p-STAT3, MCL–1, and SOCS3.

Results: The immunohistochemistry also showed a significant increase in Bax (0.29 ± 0.007 vs. 0.22 ± 0.007, P < 0.01) and Caspase-3 (0.24 ± 0.02 vs. 0.18 ± 0.006, P < 0.01) in GI group compared with Sham group, while Bax (0.26 ± 0.01 vs. 0.29 ± 0.008, P < 0.01) and Caspase-3 (0.20 ± 0.008 vs. 0.24 ± 0.02, P < 0.01) were significantly decreased by HNG-treatment compared with GI group. Along with immunohistochemistry, western blot and qRT-PCR indicated that the protein and mRNA levels of STAT3, MCL-1, and SOCS3 were up-regulated after administration of HNG at six time points after global cerebral I/R in rat.

Conclusion: HNG might exert neuroprotective effects through alleviating apoptosis and activating of SOCS3 – STAT3 – MCL-1 signal transduction pathway.

Highlights

(1) Cerebral ischemia led to neuronal loss in hippocampal CA1 region of rats.

(2) HNG had neuroprotective effects on ischemia/reperfusion rats.

(3) The protective effect of HNG might be related to the SOCS3 – STAT3 – MCL-1 pathway.

     

Blood pressure evolution in young patients with acute ischemic stroke: a new model for understanding the natural course of spontaneous hypertension?

Background: Approximately 80% of patients suffering an acute ischemic stroke develop transient hypertension. The physiopathological mechanism remains unclear. Due to the lack of vascular risk factors, young adults could be a useful model for understanding blood pressure (BP) evolution in this setting.

Methods: Patients between 18 and 55 years old admitted with an acute ischemic stroke were included. BP was evaluated during the following 48 h. Hypertension was defined as: systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg. Patients were divided into two groups: RF group included those who had a previous vascular risk factor and/or other medical condition known to affect the autonomic function; noRF group included patients without any of the previously stated conditions.

Results: Thirty-nine patients were included: mean age: 44.26 years old, 21 were males (53.8%). Mean SBP and DBP at admission were 139.77 ± 5.35 mmHg (range: 90–243) and 84.44 ± 3.02 mmHg (range: 60–128), respectively; 43.58% patients were hypertensive at admission. SBP decreased significantly during the first 48 h (p = 0.044) for the entire population. RF group has higher SBP (p = 0.009) and DBP (p = 0.011) at admission than the noRF group.

Conclusion: Most patients were normotensive at admission and BP fell spontaneously despite BP at admission. Young patients without medical conditions that could alter the autonomic system function could be a useful model for understanding acute hypertension in ischemic stroke.     

Gender differences in physical activity and health-related behaviors among stroke survivors: data from the 5th Korea National Health and Nutrition Examination Survey

Background: Physical activity and health-related behaviors are important in primary prevention of stroke and are also recommended for secondary prevention. Gender differences in physical activity and health-related behaviors have been reported in various populations and diseased states but data is lacking on stroke survivors.

Objectives: To assess gender disparities in physical activity in stroke patients and to investigate possible reasons for such disparities.

Methods: This is a cross-sectional study using nationwide data from the 5th Korean National Health and Nutrition Examination Survey (2010–2012). A total of 9539 participants (stroke (n = 170), non-stroke (n = 9369)) between the ages of 40–80, with no problems walking were included. Physical activity, smoking, and alcohol drinking of stroke survivors were assessed by gender and compared with non-stroke groups. Multiple logistic regression was used to estimate the odds ratios (ORs) for insufficient physical activity and possible explanatory variables for gender differences.

Results: Women showed higher prevalence of insufficient physical activity after adjusting for age (OR = 7.32, 95% CI: 1.89–28.32) compared to men. Medical conditions such as depression and comorbidities failed to explain the low physical activity in women with stroke but adding socioeconomic factors to the model nullified the gender difference in physical activity.

Conclusion: In order to reduce noted gender disparities in physical activity following stroke, more focused effort to increase physical activity in women, especially with lower socioeconomic status, has to be considered.     

Internal decompression for spinal stenosis (IDSS) for decompression and use of interlaminar dynamic device (CoflexTM) for stabilization in the surgical management of degenerative lumbar canal stenosis with or without mild segmental instability: our initial results

Introduction: Internal decompression of spinal stenosis (IDSS) and Posterior dynamic stabilization (PDS) form a bridge between decompression laminectomy alone and rigid fusion, by attempting to sustain beneficial effects of decompression and stabilization in an attempt to prevent bad effects of relentless degeneration.

Objective: To evaluate the clinical outcome in operated patient of posterior dynamic stabilization.

Design: Data were collected over 1 year in prospective, nonrandomized follow-up study using outcome scales.

Setting: Single surgeon, tertiary care centre in Mumbai, India.

Described here is the operative technique of posterior dynamic stabilization using CoFlex^TM and clinical outcome of 67 consecutive patients using Visual Analogue Scale and Oswestry Disability Score.     

The alliance with expanding blood volume and correcting anemia is an effective therapeutic measure for the adult anemia patients of acute cerebral infarction

Purpose/aim of the study: Various factors are believed to be involved in the etiology of cerebral infarction. Anemia has been shown to deteriorate in association with ischemic stroke. However, the exact clinical association between anemia and ischemic stroke still remains unclear. We evaluated the clinical features of adult anemia patients with acute cerebral infarction and seek a better treatment different from the other causes of cerebral infarction, and to provide a reference for the diagnosis and treatment of these anemia patients with acute cerebral infarction.

Methods: Thirty-two adult patients of acute cerebral infarction with anemia were included in this study. A primary discharge diagnosis of acute cerebral infarction with anemia was done, and all subjects were evaluated as retrospective data. The clinical features were analyzed. A chi-square test was used to analyze the associations between different variables. Therapeutic interventions and outcomes were analyzed under t-test, compared between the two groups.

Results: The NIHSS score in the patients with the administration of EBV/CA (Expanding blood volume and correcting anemia) more lowed than Non-EBV/CA in 7 days and 14 days after initial hospitalization. The mRS score in the patients with the administration of EBV/CA also more lowed than Non-EBV/CA in 14 days. Moreover, the correlation between Hb-serum-level and NIHSS scores in the time of initial hospitalization is negative significantly.

Conclusions: Anemia is associated with increased neuronal damage and deterioration of acute cerebral infarction in the adults. Expanding blood volume and correcting anemia are effective therapeutic measures in the adult patients of acute cerebral infarctions with anemia.     

Intraluminal spindle-shaped-head suture induced occlusion of middle cerebral artery in the rats

Objective: This study aimed to introduce a modified animal model of middle cerebral arterial occlusion (MCAO) through placement of intraluminal spindle-shaped head suture by comparing the traditional MCAO model.

Methods: A total of 60 male Spraque-Dawley (SD) rats were divided into two groups and MCAO was induced using spindle-shaped head suture or round head suture. The mortality, infarct volume, neurological function, success rate of the surgery, and stability of modeling were examined to evaluate the effectiveness of this model.

Results: Our results showed the success rate was 90.0% in spindle-shaped head group and 83.3% in round head group showing no significant difference; spindle-shaped head achieved a better establishment of MCAO model as shown in neurological examination. The infarct volume was 31.99 ± 5.44% in spindle-shaped head group and was significantly higher than in round head group (24.59 ± 7.17%; p < 0.05), and the coefficient of variation of infarct volume in spindle-shaped head group was lower than in round head group.

Conclusion: Our findings indicate that the modified suture induces a more reproducible and stable ischemic stroke following MCAO in SD rats.     

Possible autoantibody-negative limbic encephalitis after anterior temporal lobectomy for hippocampal sclerosis

Purpose: Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage.

Materials and methods: We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and neuroimaging findings of a damage involving the contralateral mesial temporal lobe structures.

Results: A diagnosis of a possible autoimmune encephalitis was made.

Conclusions: Due to its peculiarities (compared with other cases of bilateral temporal lesions, the damage occurred on two distinct occasions), this case might contribute to shed light on the issue of the possible contralateral reorganization of memory processes subserved by the mesial temporal lobe structures chronically involved in epileptogenesis.     

Changes in gait and plantar foot loading upon using vibrotactile wearable biofeedback system in patients with stroke

Background: Patients with stroke walk with excessive foot inversion at the affected side, which may disturb their balance and gait.

Objectives: This study aimed to investigate the effects of instant biofeedback of plantar force at the medial and lateral forefoot regions on gait and plantar foot loading in patients with stroke.

Methods: A total of eight patients with hemiplegic stroke, who had flexible rearfoot varus deformity at the affected side, participated in this study. A vibrotactile biofeedback system was developed and evaluated. It analyzed forces at the medial and lateral forefeet, and instantly provided vibration clues when the plantar force at medial forefoot was less than a threshold. Each subject’s three-dimensional gait parameters and plantar-pressure distribution during walking were measured under two experimental conditions (sequence randomized): with and without the device turned on (Trial-registration number: ChiCTR-IPB-15006530 and HKCTR-1853).

Results: Providing biofeedback significantly reduced the foot inversion and increased the mid-stance foot–floor contact area and medial midfoot plantar pressure of the affected limb, bringing the values of these parameters closer to those of the unaffected side. The biofeedback also significantly reduced the unaffected side’s excessive knee flexion and hip abduction.

Conclusions: There were signs of improved foot loading characteristics and gait upon provision of instant vibrotactile biofeedback of plantar force. The positive results of this study further support the development of wearable biofeedback devices for improving gait of patients with stroke.     

Risk factors of sleep disorder after stroke: a meta-analysis

Objective: The study aimed to evaluate potential risk factors of sleep disorder in stroke patients by conducting a meta-analysis.

Methods: Relevant articles were searched in PubMed, Medline, Springer, Elsevier, Science Direct, Cochrane Library, and Google scholar database up to May 2014. The effect size of risk factors, including gender, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol use, previous stroke, chronic obstructive pulmonary disease (COPD), and habitual snoring were measured by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The heterogeneity of effect size across studies was evaluated by applying Cochran’s Q-statistic and the I² statistic. In addition, Egger’s linear regression test was used to evaluate the publication bias.

Results: A total of 8 studies, involving 1381 stroke patients (578 patients with sleep disorder, and 803 patients without sleep disorder) were suitable for this meta-analysis. Pooled results showed significant association of sleep disorder risk in stoke patients with diabetes mellitus (OR = 1.42, 95% CI = 1.09–1.85), alcohol use (OR = 1.59, 95% CI = 1.19–2.12) and habitual snoring (OR = 14.77, 95% CI = 5.52–39.53). No significant association was found between risk of sleep disorder in stoke patients and other factors. Furthermore, heterogeneity was just presented among studies involving gender, hypertension and smoking. Egger’s linear regression test showed no statistical publication bias.

Conclusion: Diabetes mellitus, alcohol use, and habitual snoring are associated with a significantly increased risk of sleep disorder in stroke patients.

Highlights: (1) Eight studies containing 1381 patients are included in this meta-analysis.

(2) Diabetes mellitus was associated with sleep disorder in stroke patients.

(3) Alcohol use could increase the risk of sleep disorder in stroke patients.

(4) Habitual snoring was obviously associated with sleep disorder in stroke patients.

     

Pitavastatin treatment induces neuroprotection through the BDNF-TrkB signalling pathway in cultured cerebral neurons after oxygen-glucose deprivation

Objectives: Along with their lipid-lowering effect, statins have been reported to have neuroprotective function in both in vivo and in vitro models of neurodegenerative diseases. We conducted this study in order to uncover the he neuroprotective effect of the lipophilic statin pitavastatin (PTV) and investigate the underlying molecular mechanisms using primary cultured cerebral neurons exposed to oxygen-glucose deprivation (OGD).

Methods: The primary cultured cerebral neurons were randomly assigned into four groups: the control group, the pitavastatin treatment group, the OGD group and the OGD + pitavastatin treatment group. The pitavastatin’s concentration were set as follows: 1μM, 15μM, 30μM. After 3 hours OGD treatment, we use MTT method to assessment cell viability, immunofluorescence to observe neuron morphology and western blot method analysis the BDNF, TrkB.

Results: PTV at concentrations of 1 μM and 15 μM elevated the survival rate of cortical neurons exposed to OGD, whereas 30 μM PTV did not show such an effect. Moreover, PTV promoted neuronal dendrite growth at concentrations of 1 μM and 15 μM. Increased expression levels of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) were observed in both of the following two scenarios: when neurons were treated with PTV for 48 hours and when PTV was added after the OGD procedure.

Conclusion: Pitavastatin treatment induces neuroprotection in cultured cerebral neurons after oxygen-glucose deprivation this neuroprotection induced by PTV involves the BDNF-TrkB signalling pathway.