Hypoxia-inducible factor(HIF)is a pivotal transcription factor for hypoxic response.This article reviews the related characteristics of HIF-1 and its target genes vascular endothelial growth factor and the neuroprotective mechanisrms in cerebral ischemia.

Cognitive impairment caused by ischemic stroke is becoming more and more concerned.It is crucial to explore its pathophysiological mechanism and related clinical predictive indexes for understanding the occurrence,development and treatment of the disease.This article discusses the pathophysiologic mechanism of cognitive impairment after stroke from the aspects of white matter damage,amyloid abnormal deposition,blood-brain barrier damage,and synaptic plasticity injury,and reviews the risk factors,imaging and biological markers that can be used to predict cognitive impairment after stroke.

Cerebral microbleeds (CMBs) are a key biomarker of cerebral small vessel disease on magnetic resonance imaging,They have potential clinical relevance to future stroke risk.Therefore,the detection of CMBs has important clinical significance for various cerebrovascular disease phenotypes.This article briefly summarizes the detection method of CMBs,mainly investigating the clinical significance of CMBs in general population and in patients with ischemic stroke,cerebral hemorrhage,vascular cognitive impairment,cerebral amyloid angiopathy,and leukoaraiosis.

Cerebral small vessel disease (CVSD) is a group of small vascular diseases involving small arteries,arterioles,small veins,venules,and capillaries.The imaging findings were lacunar infarction,cerebral microbleeds,cerebral white matter lesions,and perivascular space expansion.In recent years,the incidence of CSVD is increasing,which brings different degree of economic burden to the families and society.It becomes the focus of research at present.The permeability change of blood-brain barrier is the main reason for the onset of CSVD.This article reviews the relationship between the integrity of blood-brain barrier and CSVD.

Cerebral small vessel disease (CSVD) refers to the syndromes of clinical,cognitive,radiographic and pathological manifestations caused by intracranial small vessel disease.Due to the insidious onset of CSVD,unknown etiology,diverse clinical manifestations,and better short-term prognosis,it is easily ignored,resulting in misdiagnosis,missed diagnosis,and non-standard diagnosis and treatment.This article reviews the advances in research on clinical manifestations,imaging features,diagnosis and treatment of CSVD.

Objective To investigate the protective effect of mild hypothermia on cerebral ischemia-reperfusion injury in rats and the effect of mild hypothermia on the expression of inhibitor of differentiation 2 (Id2) protein.Methods A total of 72 adult male rats were randomly divided into a sham operation group,a normothermia group,and a mild hypothermia group.A model of middle cerebral artery occlusion was induced by a suture method.The mild hypothermia group was treated with low temperature (anal temperature 33±1 ℃,tympanic membrane temperature 31±1 ℃).Modified Neurological Severity Score (mNSS) was used to evaluate neurological deficits,triphenyltetrazolium chloride staining was used to detect infarct volume,and Western blot was used to detect the Id2 expression in the ischemic cortex at ischemia-reperfusion 6,12,24,and 72 h,respectively.ResultsThe mNSS scores in the mild hypothermia group were significantly lower than those in the normothermia group,the infarct volumes were significantly smaller than those in the normothermia group at ischemia-reperfusion 6,12,24,and 72 h (all P<0.001).Western blot analysis showed that the Id2 expressions in the ischemic cortex in the mild hypothermia group were significantly lower than those in the normothermia group at ischemia-reperfusion 6,12,24,and 72 h (all P<0.05).Conclusion s Mild hypothermia can decrease neurological deficits and reduce infarct volume after cerebral ischemia-reperfusion,its mechanism may be associated with the down-regulation of the Id2 expression.

Objective To investigate the effect of high frequency (10 Hz),low frequency (1 Hz) and theta burst stimulation (TBS) mode of repetitive transcranial magnetic stimulation (rTMS) on the recovery of motor function in hemiplegic patients following acute ischemic stroke.Methods Seventy-two patients with hemiplegia after acute ischemic stroke were randomly grouped with the random number table.They were treated with low frequency (n=18),high frequency (n=18),and TBS (n=18) rTMS or sham stimulation (control group,n=18),once a day,for 2 weeks.Fugl-Meyer Assessment (FMA) and National Institutes of Health Stroke Scale (NIHSS) were used to evaluate neurological function in all patients before rTMS treatment (on the day before the first treatment) and after treatment (on the day after the last treatment).Results After treatment,the FMA and NIHSS scores in the 4 groups were significantly improved compared with before treatment (all P<0.05).After rTMS treatment,the FMA and NIHSS scores were improved significantly in the high frequency group,low frequency group and TBS group compare with the control group (all P<0.05).There were no significant differences among all the treatment groups.Conclusion sHigh frequency,low frequency and TBS rTMS can improve the recovery of motor function in hemiplegic patients following acute ischemic stroke.There were no significant differences among all the treatment modes.

Objective To investigate the correlation between subclinical hypothyroidism (SCH) and cerebral atherosclerosis burden in patients with large artery atherosclerotic stroke.Methods Consecutive inpatients with acute large artery atherosclerotic stroke were enrolled.SCH was defined as TSH 4.50-10.0 mU/L and serum thyroxine level was normal.Cerebral atherosclerosis burden score was used to evaluate the severity of cerebral atherosclerosis.The total score of 1 or 2 was defined as mild atherosclerosis,and >2 was defined as severe atherosclerosis.Univariate analysis and multivariate logistic regression analysis was used to evaluate the correlation between SCH and severe cerebral atherosclerosis.ResultsA total of 263 patients with large artery atherosclerotic stroke were enrolled,including SCH 62 (23.6%),mild atherosclerosis 119 (45.2%),and severe atherosclerosis 144 (54.8%).The age (63.6±10.9 years vs.60.5±11.4 years;t=2.274,P=0.024),homocysteine (17.10±6.20 μmol/L vs.15.63±5.17 μmol/L;t=2.058,P=0.041),National Institutes of Health Stroke Scale (NIHSS) score (8.0 [5.0-10.0]vs.6.0 [5.0-9.0];Z=2.059,P=0.039),as well as the proportions of patients with hypertension (72.9%vs.58.8%;χ2=5.812,P=0.016),smoking (38.2%vs.26.1%;χ2=4.366,P=0.037),and SCH (30.6%vs.15.1%;χ2=8.610,P=0.003) in the severe cerebral atherosclerosis group were significantly higher than those in the mild cerebral atherosclerosis group.Multivariate logistic regression analysis indicated that SCH was an independent risk factor for severe atherosclerosis in patients with large atherosclerotic stroke (odd ratio 3.345;95%confidence interval 1.692-6.612;P=0.001) after adjusting for age,sex,hypertension,smoking,homocysteine,and NIHSS score.ConclusionSCH is an independent risk factor for severe cerebral atherosclerosis in patients with large atherosclerotic stroke.

Ischemic stroke is one of the diseases with the highest morbidity and disability.Hypertension is recognized as the most important independent risk factor for ischemic stroke.Vascular remodeling during the development of hypertension is the pathological basis of causing ischemic stroke.Studies have shown that vascular smooth muscle cell proliferation and apoptosis will lead to vascular remodeling.In addition,cerebral ischemia-reperfusion can result in neuronal damage and apoptosis.Recent research has shown that vascular remodeling and neuronal apoptosis are associated with chloride channels.At least 3 chloride channels including volume regulated chloride channel,calcium activated chloride channel and cystic fibrosis transmembrane conductance regulator are involved in these processes.This article reviews the roles of the 3 chloride channels in vascular remodeling,neuronal apoptosis,and ischemic stroke.

Cerebral venous and sinus Thrombosis (CVST) is a rare ischemic cerebrovascular disease,the lesions of 60% patients are involved in multiple venous sinus,of which the superior sagittal sinus thrombosis is most common.The pathogenesis and pathophysiology of CVST has not yet been fully elucidated,and the establishment of stable and ideal animal models can provide a basis for the study of its development,prognosis and efficacy assessment.This article summarizes the characteristics and advantages of several available CVST models,but each method has its own limitations.Therefore,the establishment of a more ideal animal model will help to fully understand the pathogenesis and pathological process of CVST.