Secondary thalamic atrophy related to brain infarction may contribute to post-stroke cognitive impairment.

BACKGROUND AND PURPOSE: The thalamus is a key brain hub that is globally connected to many cortical regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or cognitive correlates. This study investigates associations between thalamic volumes and post-stroke cognitive function. METHODS: Participants with non-thalamic brain infarcts (3-42 months) underwent MRI and cognitive testing. Focal infarcts and thalami were traced manually. In cases with bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics were extracted using a standardized and previously validated neuroimaging pipeline. Age and gender-matched healthy controls provided normal comparative thalamic volumes. Thalamic atrophy was considered when the volume exceeded 2 standard deviations greater than the controls. RESULTS: Thalamic volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.5 cc, p < 0.001) and right (4.4 ± 1.4 vs. 5.5 ± 0.6 cc, p < 0.001) thalamic volumes in the controls. After controlling for head-size and global brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume (ß= -0.069, p=0.024). Left thalamic atrophy correlated significantly with poorer cognitive performance (ß = 4.177, p = 0.008), after controlling for demographics and infarct volumes. CONCLUSIONS: Our results suggest that the remote effect of infarction on ipsilateral thalamic volume is associated with global post-stroke cognitive impairment.

Early Use of Statin in Patients Treated with Alteplase for Acute Ischemic Stroke.

Studies have reported that statin usage before stroke can increase the incidence of intracerebral hemorrhage after thrombolytic treatment. However, whether the administration of statin at an early stage of ischemic stroke increases hemorrhage occurrence is unknown. The aim of this study was to assess the effect of statin on neurological imaging and functional outcomes after intravenous alteplase treatment, within 24 h of acute ischemic stroke attack. A total of 119 consecutive acute ischemic stroke patients treated by intravenous alteplase were recruited, of which 71 patients (59.7 %) were given statin therapy within 24 h of stroke onset. The physiological parameters, including demography, vascular risk factors, and clinical characteristics were recorded. The occurrence of intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day functional outcomes, and mortality in the patients were further analyzed. There were 24 occurrences of ICH after alteplase treatment (20.2 %) and there was no difference when patients were treated with statin (p = 0.280). Multivariate logistic regression analysis showed no significant correlation between the administration of statin and the occurrence of ICH (p = 0.230) or sICH (p = 0.949). There was a trend toward better neurological function with higher statin dose. The use of statin in the early stage of ischemic stroke is safe and does not increase the risk of intracerebral hemorrhage after alteplase treatment, suggesting that a clinical trial of early statin treatment on a large scale following thrombolysis is needed for further evaluation.

Amphiphysin-IgG autoimmune sciatic neuropathy and facial neuropathy related to primary central nervous system lymphoma: A case report.

We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.

[An analysis of risk factors for ischemic stroke of different age and gender].

OBJECTIVE: To compare distribution difference in risk factors of patients with first-ever ischemic stroke (IS) of different age and gender. METHODS: A total of 1027 patients admitted to the neurological department in Shanghai Renji Hospital with first-ever IS were recruited and divided into young adult group (< 50 years old), middle-aged group (50 - 80 years old), and very old group (> 80 years old) according to their ages. Risk factor analysis included history of smoking, high alcohol consumption, hypertension (HT), diabetes mellitus (DM), heart diseases, atrial fibrillation (AF) and family history of cardiovascular diseases. RESULTS: Female patients were globally older than male patients (71.1 vs 65.7, P < 0.001) at the first attack of IS and having higher prevalence of DM (26.8% vs 19.2%, P = 0.004), heart diseases (28.8% vs 19.2%, P < 0.001) and AF (7.6% vs 3.9%, P = 0.009). However, female patients were less likely to drink heavily (1.0% vs 31.6%, P < 0.001) or smoke (4.4% vs 59.9%, P < 0.001) than the male patients. The rates of smoking and heavy drinking in young adult group were higher than that in other two groups. Patients in very old group had higher prevalence of heart diseases and AF but lower proportion of positive family cardiovascular diseases history than patients in other two groups. HT and DM were equally frequent among three groups. In young adult group, female patients were more likely to have heart diseases and family history of heart diseases (P = 0.015 and P = 0.048). In middle-old group, HT, DM, heart disease and AF were more common in women than in men (P = 0.021, P = 0.004, P = 0.001 and P = 0.039). CONCLUSION: There are differences in risk factor distribution in patients with first-ever IS of different age and gender. Therefore, screening and health education should be performed in allusion to different risk factors.

Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction.

Recent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred risk for developing cognitive impairment. Since oligodendrocyte precursor cells participated in the white matter repair and remodeling after ischemic brain injury, we explored whether hyperglycemia induced neurobehavioral deficits were associated with dysfunction of oligodendrocyte precursor cells. Adult male C57BL/6 mice (n = 40) were randomly divided into 4-week diabetes, 8-week diabetes, and control groups. Experimental diabetic mice were induced by streptozotocin injection. Learning and cognitive function, exploratory, anxiety and depression behaviors were assessed by Morris water maze, open field test, elevated plus maze, and tail suspension test, respectively. Immunofluorescence staining of neuron-glial antigen 2 and myelin basic protein were performed. Oligodendrocyte precursor cells were cultured in different glucose level to explore possible mechanism in vitro. The learning and cognitive function of 4-week and 8-week diabetic mice were attenuated compared to the control group (p < 0.05). The diabetic mice had less exploratory behavior compared to the control (p < 0.05). However, the diabetic mice were more likely to show anxiety (p < 0.05) and depression (p < 0.01) compared to the control. Further study demonstrated the number of oligodendrocyte precursor cells and the level of myelin basic protein expression were decreased in diabetic mice and the migration and survival ability were suppressed in the hyperglycemic environment in vitro (p < 0.05). Our results demonstrated that diabetes mellitus induced neurological deficits were associated with the decreased number and dysfunction of oligodendrocyte precursor cells.

Distinct roles of right temporoparietal cortex in pentagon copying test.

Pentagon Copying Test (PCT) is commonly used to assess visuospatial deficits, but the neural substrates underlying pentagon copying are not well understood. The Qualitative Scoring Pentagon Test (QSPT), an optimized scoring system, classifies five categories of errors patients make in pentagons copying and grades them depending on the errors' severity. To determine the strategic brain regions involved in the PCT, we applied the QSPT system to evaluate the visuospatial impairment of 136 acute ischemic stroke patients on the PCT and used Support Vector Regression Lesion-Symptom Mapping to investigate relevant brain regions. The total QSPT score was correlated with the right supramarginal gyrus. The angle number errors and closure errors were principally associated with lesions of the posterior temporoparietal cortex, including the right middle occipital gyrus and middle temporal gyrus, while the intersection errors and rotation errors were related to the more anterior part of the right temporoparietal lobe with the additional frontal cortex. In conclusion, the right temporoparietal cortex is the strategic region for pentagon copying tasks. The angle number and closure represent the visuospatial processing of within-object features, while intersection and rotation require between-object manipulation. The posterior-anterior distinction in the right temporoparietal region underlies the differences of within-object and between-object processing.

Oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination via Wnt/ß-catenin pathway in a mouse model of middle cerebral artery occlusion.

White matter injury is a critical pathological characteristic during ischemic stroke. Oligodendrocyte precursor cells participate in white matter repairing and remodeling during ischemic brain injury. Since oligodendrocyte precursor cells could promote Wnt-dependent angiogenesis and migrate along vasculature for the myelination during the development in the central nervous system, we explore whether exogenous oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination after middle cerebral artery occlusion in mice. Here, oligodendrocyte precursor cell transplantation improved motor and cognitive function, and alleviated brain atrophy. Furthermore, oligodendrocyte precursor cell transplantation promoted functional angiogenesis, and increased myelin basic protein expression after ischemic stroke. The further study suggested that white matter repairing after oligodendrocyte precursor cell transplantation depended on angiogenesis induced by Wnt/ß-catenin signal pathway. Our results demonstrated a novel pathway that Wnt7a from oligodendrocyte precursor cells acting on endothelial ß-catenin promoted angiogenesis and improved neurobehavioral outcomes, which facilitated white matter repair and remodeling during ischemic stroke.

Modified cerebral small vessel disease score is associated with vascular cognitive impairment after lacunar stroke.

We conducted a cross-sectional study to characterize the relationship between total and modified small vessel disease (SVD) score with vascular cognitive impairment (VCI). Patients (n = 157) between the ages of 50 and 85 years old who had suffered their first lacunar infarction were analyzed prospectively. Brain magnetic resonance imaging was performed to identify SVD manifestations, which were used to calculate total or modified SVD scores. Neuropsychological assessments measured cognitive function. Spearman correlation analysis demonstrated that the total and modified SVD scores were associated with overall cognition as well as with function in the executive and visuospatial domains. The associations remained significant in linear regression after adjusting for age, sex, education and vascular risk factors. Binary logistic regression and chi-squared trend tests revealed that VCI risk increased significantly with SVD burden based on the modified SVD score. Subsequent chi-squared testing demonstrated that the VCI rate was significantly higher in patients with a modified SVD score of 5-6 than in patients without any SVD burden. Our results suggest that both the total and modified SVD scores show a negative association with cognitive function, but the modified SVD score may be better at identifying patients at high VCI risk.

[Impacts of stroke clinics on the utilization of statins for secondary prevention of ischemic stroke].

OBJECTIVE: To describe the impact of stroke clinic on the usage of statins for secondary prevention of ischemic stroke. METHODS: Data about the demography, social economic status, personal histories, blood lipid profiles, and the status of the usage of statins from 568 serial ischemic stroke patients were retrospectively analysed. RESULTS: A total of 51.3% patients followed up in stroke clinic (306 patients) and 7.6% patients followed up in general clinic (262 patients) were treated with statins. 71.6% patients with and 44.8% patients without hyperlipidemia in stroke clinics were taking statins, which were higher than that patients in the general clinics (27.1% and 2.0% respectively). The patients in the stroke clinics with high LDL-C level (>3.4 mmol/L) were more likely to be treated with statins than those with lower level (25.6% vs 14.7%, P=0.017). CONCLUSIONS: The rate of statins usage is extremely low in stroke patients followed up in a general clinic, but it can been improved greatly in a stroke clinic. Stroke clinic can narrow the gap between the clinical practice and the guideline for secondary prevention of ischemic stroke.

Oligodendrocyte precursor cells transplantation protects blood-brain barrier in a mouse model of brain ischemia via Wnt/ß-catenin signaling.

Blood-brain barrier damage is a critical pathological feature of ischemic stroke. Oligodendrocyte precursor cells are involved in maintaining blood-brain barrier integrity during the development. However, whether oligodendrocyte precursor cell could sustain blood-brain barrier permeability during ischemic brain injury is unknown. Here, we investigate whether oligodendrocyte precursor cell transplantation protects blood-brain barrier integrity and promotes ischemic stroke recovery. Adult male ICR mice (n = 68) underwent 90 min transient middle cerebral artery occlusion. After ischemic assault, these mice received stereotactic injection of oligodendrocyte precursor cells (6 × 105). Oligodendrocyte precursor cells transplantation alleviated edema and infarct volume, and promoted neurological recovery after ischemic stroke. Oligodendrocyte precursor cells reduced blood-brain barrier leakage via increasing claudin-5, occludin and ß-catenin expression. Administration of ß-catenin inhibitor blocked the beneficial effects of oligodendrocyte precursor cells. Wnt7a protein treatment increased ß-catenin and claudin-5 expression in endothelial cells after oxygen-glucose deprivation, which was similar to the results of the conditioned medium treatment of oligodendrocyte precursor cells on endothelial cells. We demonstrated that oligodendrocyte precursor cells transplantation protected blood-brain barrier in the acute phase of ischemic stroke via activating Wnt/ß-catenin pathway. Our results indicated that oligodendrocyte precursor cells transplantation was a novel approach to the ischemic stroke therapy.

Structural brain network measures are superior to vascular burden scores in predicting early cognitive impairment in post stroke patients with small vessel disease.

OBJECTIVES: In this cross-sectional study, we aimed to explore the mechanisms of early cognitive impairment in a post stroke non-dementia cerebral small vessel disease (SVD) cohort by comparing the SVD score with the structural brain network measures. METHOD: 127 SVD patients were recruited consecutively from a stroke clinic, comprising 76 individuals with mild cognitive impairment (MCI) and 51 with no cognitive impairment (NCI). Detailed neuropsychological assessments and multimodal MRI were performed. SVD scores were calculated on a standard scale, and structural brain network measures were analyzed by diffusion tensor imaging (DTI). Between-group differences were analyzed, and logistic regression was applied to determine the predictive value of SVD and network measures for cognitive status. Mediation analysis with structural equation modeling (SEM) was used to better understand the interactions of SVD burden, brain networks and cognitive deficits. RESULTS: Group difference was found on all global brain network measures. After adjustment for age, gender, education and depression, significant correlations were found between global brain network measures and diverse neuropsychological tests, including TMT-B (r = -0.209, p < .05), DSST (r = 0.206, p < .05), AVLT short term free recall (r = 0.233, p < .05), AVLT long term free recall (r = 0.264, p < .05) and Rey-O copy (r = 0.272, p < .05). SVD score showed no group difference and was not correlated with cognition tests. Network global efficiency (EGlobal) was significantly related to cognitive state (p < .01) but not the SVD score. Mediation analysis showed that the standardized total effect (p = .013) and the standardized indirect effect (p = .016) of SVD score on cognition was significant, but the direct effect was not. CONCLUSIONS: Brain network measures, but not the SVD score, are significantly correlated with cognition in post-stroke SVD patients. Mediation analysis showed that the cerebral vascular lesions produce cognitive dysfunction by interfering with the structural brain network in SVD patients. The brain network measures may be regarded as direct and independent surrogate markers of cognitive impairment in SVD.

MicroRNA-126 Regulates Angiogenesis and Neurogenesis in a Mouse Model of Focal Cerebral Ischemia.

Studies demonstrate that microRNA-126 plays a critical role in promoting angiogenesis. However, its effects on angiogenesis following ischemic stroke are unclear. Here, we explored the effect of microRNA-126-3p and microRNA-126-5p on angiogenesis and neurogenesis after brain ischemia. We demonstrated that both microRNA (miRNA)-126-3p and microRNA-126-5p increased the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with the scrambled miRNA control (p < 0.05). Transferring microRNA-126 into a mouse middle cerebral artery occlusion model via lentivirus, we found that microRNA-126 overexpression increased the number of CD31+/BrdU+ (5-bromo-2'-deoxyuridine-positive) proliferating endothelial cells and DCX+/BrdU+ neuroblasts in the ischemic mouse brain, improved neurobehavioral outcomes (p < 0.05), and reduced brain atrophy volume (p < 0.05) compared with control mice. Western blot results showed that AKT and ERK signaling pathways were activated in the lentiviral-microRNA-126-treated group (p < 0.05). Both PCR and western blot results demonstrated that tyrosine-protein phosphatase non-receptor type 9 (PTPN9) was decreased in the lentiviral-microRNA-126-treated group (p < 0.05). Dual-luciferase gene reporter assay also showed that PTPN9 was the direct target of microRNA-126-3p and microRNA-126-5p in the ischemic brain. We demonstrated that microRNA-126-3p and microRNA-126-5p promoted angiogenesis and neurogenesis in ischemic mouse brain, and further improved neurobehavioral outcomes. Our mechanistic study further showed that microRNA-126 mediated angiogenesis through directly inhibiting its target PTPN9 and activating AKT and ERK signaling pathways.

Dynamic Detection of Thrombolysis in Embolic Stroke Rats by Synchrotron Radiation Angiography.

A rodent model of embolic middle cerebral artery occlusion is used to mimic cerebral embolism in clinical patients. Thrombolytic therapy is the effective treatment for this ischemic injury. However, it is difficult to detect thrombolysis dynamically in living animals. Synchrotron radiation angiography may provide a novel approach to directly monitor the thrombolytic process and assess collateral circulation after embolic stroke. Thirty-six adult Sprague-Dawley rats underwent the embolic stroke model procedure and were then treated with tissue plasminogen activator. The angiographic images were obtained in vivo by synchrotron radiation angiography. Synchrotron radiation angiography confirmed the successful establishment of occlusion and detected the thrombolysis process after the thrombolytic treatment. The time of thrombolytic recanalization was unstable during embolic stroke. The infarct volume increased as the recanalization time was delayed from 2 to 6 h (p < 0.05). The collateral circulation of the internal carotid artery to the ophthalmic artery, the olfactory artery to the ophthalmic artery, and the posterior cerebral artery to the middle cerebral artery opened after embolic stroke and manifested different opening rates (59%, 24%, and 75%, respectively) in the rats. The opening of the collateral circulation from the posterior cerebral artery to the middle cerebral artery alleviated infarction in rats with successful thrombolysis (p < 0.05). The cerebral vessels of the circle of Willis narrowed after thrombolysis (p < 0.05). Synchrotron radiation angiography provided a unique tool to dynamically detect and assess the thrombolysis process and the collateral circulation during thrombolytic therapy.

[The prevalence and risk factors for cognitive impairment following ischemic stroke].

OBJECTIVES: To identify the prevalence and risk factors that were associated with post-stroke cognitive impairment (PSCI) among a large cohort of consecutive ischemic stroke patients. METHODS: 526 consecutive patients, who had suffered from ischemic stroke 3 months ago were recruited in this study. Patients were classified as having no cognitive impairment (NCI), cognitive impairment but no dementia (CIND) and vascular dementia (VaD) according to their cognitive function. They were also categorized as with subcortical ischemic vascular diseases (SIVD) or cortical ischemic vascular diseases (CIVD) with neuroimaging findings. Their demographic data, vascular risk factors and stroke characteristics were also documented. RESULTS: The overall prevalence of PSCI (CIND + VaD) was 36.7%. Compared with the NCI subjects, PSCI subjects were older, more dominant femininely, less educated, with more cases of right hemi-paralysis and higher depression scores, but did not have more specific vascular risk factor. Separately, VaD patients demonstrated lower economic level, less spouse-caring, more prevalence of dysphasia, higher rate of incontinence and more cases with CIVD, while CIND patients had more cases with SIVD. The VaD patients had more cortical lesions and lower depression scores than the CIND patients. On logistic regression analysis, older age, female gender, lower economic level, dysphasia, SIVD, CIVD and higher depression scores were independent risk factors for PSCI. CONCLUSION: PSCI is common among ischemic stroke patients and related to demographic factors, stroke types, and depression.

Blood-Brain Barrier Disruption Induced Cognitive Impairment Is Associated With Increase of Inflammatory Cytokine.

Patients with diabetes suffer the higher risk of dementia and the underlying pathological mechanism of cognitive dysfunction in diabetes is not fully understood. In this study, we explore whether the cognitive impairment in the diabetic rat is associated with increased blood brain barrier (BBB) permeability and the change of the inflammatory cytokine. Experimental diabetic rats were induced by single intraperitoneal injection of streptozotocin (STZ). Cognitive function was evaluated by Morris water maze in the normal and the diabetic rats, respectively. The spatial acquisition trials were conducted over five consecutive days and the probe test was performed on day 6, followed by working memory test on the next 4 days. Escape latency was recorded in the acquisition trials and working memory test; time spent in the target quadrant and the number of crossing the former platform were recorded in the probe test. BBB permeability was assessed by measuring the extravasation of IgG. The image of occludin and claudin-5 staining by a confocal microscope were acquired to measure the gap in the tight junction. Cytokines TNF-α, IL-1ß and IL-6 mRNA expression were further examined by Real-time PCR. The time spent in the target quadrant within 30 s decreased in the 8-week STZ rats compared to that of the normal rats (p < 0.05), while no difference was seen in the performance of working memory between the diabetic and normal rats. IgG leakage significantly increased in the brain parenchyma of the 8-week STZ rats compared to the normal rats (p < 0.05). The immunostaining of occludin and claudin-5 suggested the gap in the tight junction increased in the 8-week STZ rats compared to the normal rats (p < 0.05). Moreover, TNF-α and IL-6 mRNA also increased in the brain of 8-week STZ rats compared to the normal rats (p < 0.05). These results suggested that loss of BBB integrity might contribute to progressive impairment of cognitive in the diabetic rats. The increase of TNF-α and IL-6 expression might trigger the disruption of BBB in the brain, which eventually caused cognitive impairment in the 8-week STZ rats.

[The impact of stroke clinic on improving the compliance with the guidelines for secondary prevention of ischemic stroke].

OBJECTIVE: With the physician training program and stroke clinic, the gap between clinical practice and the guideline for secondary prevention of ischemic stroke can been narrowed. METHODS: 305 patients with ischemic stroke were enrolled in a stroke clinic after their discharge from the hospital. Among the 305 patients, 87 were discharged before the institution of a physician training program (pre-training group) and 218 after the institution (post-training group). Their usage of antithrombotic agents, statins, non-standardized therapies and antihypertensive agents were compared at the time of discharge from the hospital and follow-up in the stroke clinic comparison was also made for the two groups of patients discharged before and after the physician training program. RESULTS: After the physician training program, implementation rates increased for antithrombotic agents (79.3% vs 93.1%, P < 0.01) and statins (19.5% vs 59.2%, P < 0.01), using of non-standardized therapies decreased (47.1% vs 27.5%, P = 0.001), but no change was found for using of antihypertensive agents (88.4% vs 94.0%, P > 0.05). Comparing with the usage of medications at the time of discharge, the usage of antithrombotic agents and statins after discharge i,e. in the stroke clinic were further increased (for antithrombotics, in the pre-training group 79.3% vs 86.2%, P = 0.229, in the post-training group 93.1% vs 94.0%, P = 0.696; for statins, in the pre-training group 19.5% vs 39.1%, P = 0.005, in the post-training group 59.2% vs 69.7%, P = 0.021), while the usage of non-standardized therapies decreased further (in the pre-training group 47.1% vs 17.2%, P < 0.01, in the post-training group 27.5% vs 14.2%, P = 0.001). Implement of guideline at discharge influenced the compliance as the patients with high rates of usage of antithrombotic agents and statins at the time of discharge had also high rates of the usage of them at follow-up in the stroke clinic. CONCLUSIONS: Physician training program increases the implement of the guideline for secondary stroke prevention and stroke clinic can improve the compliance with it. Usage of medications at the time of discharge influences the compliance with them during the follow-up period.

Simultaneous Imaging of Cerebrovascular Structure and Function in Hypertensive Rats Using Synchrotron Radiation Angiography.

Hypertension has a profound influence on the structure and function of blood vessels. Cerebral vessels undergo both structural and functional changes in hypertensive animals. However, dynamic changes of cerebrovasculature and the factors involved in this process are largely unknown. In this study, we explored the dynamic changes of vascular structure in hypertensive rats using novel synchrotron radiation angiography. Twenty-four spontaneously hypertensive rats (SHR) and 24 Sprague-Dawley (SD) rats underwent synchrotron radiation (SR) angiography. Each group had 8 animals. We studied the cerebral vascular changes in SHR over a time period of 3-12-month and performed quantitative analysis. No vascular morphology differences between SHR and SD rats were observed in the early stage of hypertension. The number of twisted blood vessels in the front brain significantly increased at the 9- and 12-month observation time-points in the SHR compared to the SD rats (p < 0.01). The vessel density of the cortex and the striatum in SHR was consistently higher than that in SD rats at time points of 3-, 9-, and 12-month (p < 0.001). Vascular elasticity decreased both in SHR and SD rats with aging. There were statistically significant differences in the relative vascular elasticity of extracranial/intracranial internal carotid artery, middle cerebral artery, posterior cerebral artery and anterior cerebral artery between SHR and SD rats at 12-month (p < 0.01). We concluded that the dynamic vascular alterations detected by SR angiography provided novel imaging data for the study of hypertension in vivo. The longer the course of hypertension was, the more obvious the vascular differences between the SHR and the SD rats became.

Endothelial progenitor cells transplantation attenuated blood-brain barrier damage after ischemia in diabetic mice via HIF-1α.

BACKGROUND: Blood-brain barrier impairment is a major indicator of endothelial dysfunction in diabetes. Studies showed that endothelial progenitor cell (EPC) transplantation promoted angiogenesis and improved function recovery after hind limb ischemia in diabetic mice. The effect of EPC transplantation on blood-brain barrier integrity after cerebral ischemia in diabetic animals is unknown. The aim of this study is to explore the effect of EPC transplantation on the integrity of the blood-brain barrier after cerebral ischemia in diabetic mice. METHODS: EPCs were isolated by density gradient centrifugation and characterized by flow cytometry and immunostaining. Diabetes was induced in adult male C57BL/6 mice by a single injection of streptozotocin at 4 weeks before surgery. Diabetic mice underwent 90-minute transient middle cerebral artery occlusion surgery and received 1 × 106 EPCs transplantation immediately after reperfusion. Brain infarct volume, blood-brain barrier permeability, tight junction protein expression, and hypoxia inducible factor-1α (HIF-1α) mRNA level were examined after treatment. RESULTS: We demonstrated that neurological deficits were attenuated and brain infarct volume was reduced in EPC-transplanted diabetic mice after transient cerebral ischemia compared to the controls (p < 0.05). Blood-brain barrier leakage and tight junction protein degradation were reduced in EPC-transplanted mice (p <0.05). EPCs upregulated HIF-1α expression while HIF-1α inhibitor PX-478 abolished the beneficial effect of EPCs. CONCLUSIONS: We conclude that EPCs protected blood-brain barrier integrity after focal ischemia in diabetic mice through upregulation of HIF-1α signaling.

Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke.

Recent studies have demonstrated that exosomal microRNAs (miRNAs) are novel biomarkers and therapeutic targets for various diseases including vascular disease. However, specific exosomal miRNAs expression in stroke patients has not been reported yet. Here, we explored whether circulating exosomal miRNAs can serve as potential biomarkers for the diagnosis of acute ischemic stroke and discussed the potential for clinical application. Blood samples were collected from acute ischemic stroke patients within the first 72 h (n = 50). Circulating exosomes were exacted by Exoquick exosome isolation kit and characterized by transmission electron microscopy. Western blot was performed to assess the expression of exosomal protein makers. Exosomal miRNA-223 (miR-223) was detected by RT-PCR assay. The relationship between the expression levels of miR-223 and National Institutes of Health Stroke Scale (NIHSS) scores, brain infarct volume, and neurological outcomes were analyzed. Circulating exosomes were isolated and the size of vesicles ranged between 30 and 100 nm. The identification of exosomes was further confirmed by the detection of specific exosomal protein markers CD9, CD63, and Tsg101. Exosomal miR-223 in acute ischemic stroke patients was significantly upregulated compared to control group (p < 0.001). Exosomal miR-223 level was positively correlated with NIHSS scores (r = 0.31, p = 0.03). Exosomal miR-223 expression in stroke patients with poor outcomes was higher than those with good outcomes (p < 0.05). Increased exosomal miR-223 was associated with acute ischemic stroke occurrence, stroke severity, and short-term outcomes. Future studies with large sample are needed to assess the clinical application of exosomal miR-223 as a novel biomarker for ischemic stroke diagnosis.

Age- and gender-specific prevalence of risk factors in patients with first-ever ischemic stroke in china.

Background. Evidences are accumulating that age and gender have great impact on the distribution of stroke risk factors. Such data are lacking in Chinese population. Methods. 1027 patients with first-ever ischemic stroke (IS) were recruited and divided into young adult (<50 years), middle-aged (50∼80 years), and very old (>80 years) groups according to stroke onset ages. Vascular risk factors were collected and compared among groups. Results. Female patients were globally older than male patients at stroke onset and having higher prevalence of diabetes mellitus (DM), heart diseases, and atrial fibrillation (AF). However, females were less likely to drink heavily or smoke than males. Young patients had a much higher proportion of smoking and drinking than middle-aged and very old patients and the highest family history of hypertension, while very old patients had the highest prevalence of heart diseases and AF but lowest proportion of positive family history of vascular diseases. Hypertension and DM were equally frequent among three groups. Conclusion. Our study showed that vascular risk factors had a specific age and gender distribution pattern in Chinese IS patients. Secondary prevention strategy should emphasize on the control of different risk factors based on patient's age and gender.