T淋巴细胞在缺血性脑损伤中的作用

缺血性脑损伤程度与卒中的病死率和致残率密切相关,如何最大程度地限制缺血性脑损伤,促进神经功能恢复,是当今神经科学领域十分关注的研究热点之一.大量研究表明,多种因素参与了缺血性脑损伤的病理过程.其中,T淋巴细胞介导的免疫炎症反应在缺血性脑损伤中的作用越来越受到关注,文章主要综述了T细胞在缺血性脑损伤中的作用.     

调节性T淋巴细胞与缺血性卒中

卒中是一种高致死率和高致残率的脑血管病类型,其中缺血性卒中约占80％.目前认为,炎症机制在缺血性卒中的病理生理学进展中发挥重要作用.外周T淋巴细胞在脑缺血后24 h内浸润受损区域,参与脑组织炎症过程的进展.作为T淋巴细胞的一个亚群,调节性T细胞主要定位于缺血半暗带,但目前对其在缺血性脑损伤中的作用仍存在着争议.研究调节性T细胞在脑缺血中的作用机制,有助于进一步认识缺血性卒中的发病机制和发现新的治疗靶点.     

微小RNA miR-124在脑缺血中的作用

微小RNA(microRNA,miRNA)是一类高度保守的单链非编码小RNA,通过对mRNA的降解和(或)抑制翻译参与对目标基因的调控.作为在中枢神经系统中含量最丰富的miRNA,miR-124近来受到普遍关注.最近的研究表明,miR-124与缺血性脑损伤密切相关,但其具体调控机制尚不明确.文章对miR-124在缺血性脑损伤中的作用进行了综述.     

AMPA受体与缺血性脑损伤

α 氨基 3 羟基 4异恶唑 丙酸 (AMPA)受体介导的兴奋毒性在缺血性脑损伤的发生机制中占有重要地位。文章就近年来AMAP受体结构和通道性能在缺血性脑损伤中的作用及AMPA受体拮抗剂对缺血性脑损伤保护作用的研究作了综述     

中药对缺血性脑损伤保护作用的分子机制研究进展

缺血性脑血管病是威胁人类健康最严重的疾病之一.随着医学和分子生物学技术的迅猛发展,对缺血性脑损伤的病理生理研究越来越深入,中药对缺血性脑损伤的保护机制的研究方面也从整体水平深入到了细胞和分子水平,并取得了一定的成效.现将近几年来中药对缺血性脑损伤保护作用的分子机制研究综述如下.     

转化生长因子β1与脑缺血

转化生长因子β1（TGF-β1）是一种参与缺血性脑损伤病理生理学过程的多功能细胞因子.文章就TGF-β1的生物学作用、信号调节和在缺血性脑损伤中的表达和神经保护作用机制等做了综述.     

Toll样受体4信号转导通路及其在缺血性卒中中的作用

缺血性卒中常伴有炎症反应.研究表明,Toll样受体4(Toll-like receptor 4,TLR4)介导了缺血性卒中的发生、发展和继发性脑损伤.文章综述了TLR4信号转导通路及其在缺血性卒中中的作用,以期为开发以TLR4为靶点的治疗药物提供一定依据.     

急性缺血性卒中转归的血清生物标志物

血清生物标志物在预测急性缺血性卒中的严重程度、早期神经功能恶化和转归方面具有重要作用.了解这些血清生物标志物的种类、作用机制以及与急性缺血性脑损伤的相关性,有助于急性缺血性卒中患者的早期转归预测并指导治疗.     

单核细胞趋化蛋白-1与缺血性卒中

炎症反应在缺血性卒中的发生和发展过程中起着重要作用.单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)是趋化因子CC类哑家族成员之一,可趋化和激活单核细胞、T细胞等多种细胞,促进细胞因子表达,参与缺血性脑损伤的发生.文章对MCP-1与缺血性卒中相关的研究进展做了综述.     

What animal models have taught us about the treatment of acute stroke and brain protection

Stroke research has progressed in leaps and bounds in the past decades. A driving force is the increasing availability of new research tools in this field (eg, animal stroke models). Animal stroke models have been extensively applied to advance our understanding of the mechanisms of ischemic brain injury and to develop novel therapeutic strategies for reducing brain damage after a stroke. Animal stroke models have been useful in characterizing the molecular cascades of injury processes. These “injury pathways” are also the targets of therapeutic interventions. The major achievements made in the past 2 decades applying animal stroke models include 1) the identification of the mediator role of excitotoxin and oxygen free radicals in ischemic brain injury; 2) the confirmation of apoptosis as a major mechanism of ischemic cell death; 3) the characterization of postischemic gene expression; 4) the delineation of postischemic inflammatory reaction; 5) the application of transgenic mice to confirm the roles of purported mediators in ischemic brain injury; 6) development of novel magnetic resonance imaging sequences for early noninvasive detection of ischemic brain lesions; and, 7) the development of novel therapeutic strategies based on preclinical findings derived from animal stroke models.     

Role of Inflammation and Its Mediators in Acute Ischemic Stroke

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies.     

补体与缺血性脑血管病

缺血性脑血管病的发病率、致残率和病死率都很高。越来越多的研究表明,补体系统在脑缺血再灌注损伤中起着重要作用,而抑制补体能改善卒中的预后。文章就脑内补体的来源、在脑缺血时的作用以及缺血性脑损伤后针对补体进行治疗做了综述。     

Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice

Cyclooxygenase-2 (COX-2), a prostanoid-synthesizing enzyme that contributes to the toxicity associated with inflammation, has recently emerged as a promising therapeutic target for several illnesses, ranging from osteoarthritis to Alzheimer's disease. Although COX-2 has also been linked to ischemic stroke, its role in the mechanisms of ischemic brain injury remains controversial. We demonstrate that COX-2-deficient mice have a significant reduction in the brain injury produced by occlusion of the middle cerebral artery. The protection can be attributed to attenuation of glutamate neurotoxicity, a critical factor in the initiation of ischemic brain injury, and to abrogation of the deleterious effects of postischemic inflammation, a process contributing to the secondary progression of the damage. Thus, COX-2 is involved in pathogenic events occurring in both the early and late stages of cerebral ischemia and may be a valuable therapeutic target for treatment of human stroke.     

Alcohol‐Induced Exacerbation of Ischemic Brain Injury: Role of NAD(P)H Oxidase

Background: Chronic alcohol consumption increases ischemic stroke and exacerbates ischemic brain injury. We determined the role of NAD(P)H oxidase in exacerbated ischemic brain injury during chronic alcohol consumption. Methods: Sprague Dawley rats were fed a liquid diet with or without alcohol (6.4% v/v) for 8 weeks. We measured the effect of apocynin on 2‐hour middle cerebral artery occlusion (MCAO)/24‐hour reperfusion‐induced brain injury. In addition, superoxide production and expression of NAD(P)H oxidase subunit, gp91phox, in the peri‐infarct area were assessed. Results: Chronic alcohol consumption produced a larger infarct volume, worse neurological score, and higher superoxide production. Acute (5 mg/kg, ip, 30 minutes before MCAO) and chronic treatment with apocynin (7.5 mg/kg/d in the diet, 4 weeks prior to MCAO) reduced infarct volume, improved neurological outcome, and attenuated superoxide production in alcohol‐fed rats. Expression of gp91phox at basal conditions and following ischemia/reperfusion was greater in alcohol‐fed rats compared to non‐alcohol‐fed rats. In addition, neurons are partially responsible for upregulated gp91phox during alcohol consumption. Conclusions: Our findings suggest that NAD(P)H oxidase may play an important role in exacerbated ischemic brain injury during chronic alcohol consumption.     

Potential role of neuroprotective agents in the treatment of patients with acute ischemic stroke

Opinion statement Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none have been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.     

Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage

Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.