针刺对缺血缺氧性脑病神经细胞和神经营养因子的影响

针刺抑制缺血缺氧性脑损伤后的神经元凋亡，促进缺血缺氧性脑损伤后内源性神经干细胞的增殖和各种神经营养因予分泌的机制。     

大鼠皮质神经细胞原代培养及缺氧缺糖性损害对其损伤的研究

急性缺血缺氧性脑损伤的发病率、致残率和病死率都很高,严重危害人类健康,因此,对其发病机制的研究和有效治疗方案的探索一直是研究的热点.但在体实验往往受到体液、呼吸、循环等复杂因素的影响,很难解释某单一因素的影响作用及强度.因此探索体外培养方法,建立缺氧缺糖损伤模型,对研究脑神经细胞的缺血缺氧性损害是十分必要的,是神经科学研究中一项不可缺少的手段.     

脑红蛋白与缺血缺氧性脑损伤

脑红蛋白(neuroglobin,Ngb)是携氧球蛋白家族成员之一,主要以单体形式存在于神经细胞中,与脑内氧供应密切相关.脑缺血缺氧能诱导Ngb高表达,并作为一种内源性神经保护因子保护神经元免受缺血缺氧性损害.文章对Ngb的分布、结构、功能及其在缺血缺氧性脑损伤中的保护作用和机制做了综述.     

脑电非线性分析评价缺氧缺血性脑损伤引起的意识障碍

目的用脑电非线性分析方法中的多个参数定量评价缺血缺氧性脑损伤患者意识障碍的程度,从而探讨多种刺激状态下脑电非线性特性的变化规律,以及这些措施对意识障碍水平评估的作用。方法选取2008年-2010年宣武医院神经康复科患者60例,缺血缺氧性脑损伤后意识障碍的患者为病例组（30例）,脑卒中后意识正常的患者为对照组（30例）。所有患者依次采集安静闭眼、听觉刺激（声音刺激和音乐刺激）、痛觉刺激（针刺患侧、健侧）状态下的脑电信号,并计算脑电信号的关联维数、复杂度及近似熵非线性指数。结果病例组所有脑区在不同刺激状态下关联维数、复杂度及近似熵指数均明显低于对照组（P〈0．05）;对照组在听觉刺激及痛觉刺激状态下非线性指数高于安静闭眼状态（P〈0．05）;病例组在听觉刺激和痛觉刺激下非线性指数与安静闭眼状态无明显差异。结论脑电非线性分析可以定量评价缺血缺氧性脑损伤意识障碍的严重程度,得出不同刺激状态下大脑功能活动的变化信息,可以为评估意识障碍患者的预后及促醒措施提供新的依据。     

核因子κB在缺血缺氧性脑损伤中的作用

缺血缺氧性脑损伤是一种多因素参与的病理过程,其中炎症细胞和炎症分子起了关键作用.作为一种可以调节多种炎症分子转录的转录因子,核因子κB已经成为近期研究的热点.本文着重综述了缺血缺氧引起的海马区神经元死亡,缺血/再灌注损伤,半暗区神经元损伤及神经细胞凋亡机制与核因子κB之间的关系.     

新生大鼠缺血缺氧后胶质性谷氨酸转运体的表达及GM1的干预研究

目的探讨新生大鼠缺血缺氧性脑损伤后胶质性谷氨酸转运体的表达及神经节苷脂（GM1）的干预作用。方法通过建立新生大鼠缺血缺氧性脑损伤动物模型，应用免疫组化方法，观察缺血缺氧后不同时期大脑皮质胶质性谷氨酸转运体EAATI、EAAT2的动态表达度GM1对其表达的影响。结果缺血缺氧后6hEAAT1的表达开始上升、第2d达高峰，第3d恢复到假手术组水平；EAAT2的表达在缺血缺氧后12h开始上升，第3d达高峰，第5d恢复到假手术组水平；GM1干预组脑组织损伤明显减轻，EAAT1和EAAT2的表达较单纯缺血缺氧组显著增加（P〈0．01），持续时间延长。结论缺血缺氧诱导胶质性谷氨酸转运体的表达，GM1提高胶质性谷氨酸转运体的表达可能是GM1脑保护作用的重要机制之一。     

脉络宁对新生大鼠缺氧缺血性脑损伤后nNOS和c-Fos表达的影响

目的:检测新生大鼠缺血缺氧后神经元型一氧化氮合酶(nNOS)和c-Fos免疫活性表达改变及脉络宁对其的影响。方法:结扎7d龄大鼠右侧颈总动脉1h,然后暴露在8%氧和92%氮的混合气体中2h,建立缺氧缺血脑损伤模型。用免疫组织化学方法检测并比较缺血缺氧后和脉络宁处理后c-Fos和nNOS的免疫活性。结果:缺血缺氧6h后c-Fos表达达高峰;与缺氧缺血组相比,脉络宁处理组c-Fos阳性神经元数量增加,表达c-Fos的时间延长;与假手术组相比,缺氧缺血组nNOS表达水平增高,脉络宁处理组则下降。结论:脉络宁可抑制nNOS表达,增强c-Fos表达,可能对缺血缺氧性脑损伤有保护作用。     

亚低温治疗缺血性卒中:从实验向临床转化

作为一种神经保护措施,亚低温在临床实践中的应用与研究已非常广泛.许多疾病,如心脏停搏后脑损伤、新生儿缺血缺氧性脑病等,应用亚低温治疗已取得了肯定的疗效.虽然亚低温在治疗缺血性卒中方面已有大量动物实验和临床研究,而且动物实验已证实其具有确切的神经保护作用,但在临床研究中亚低温治疗缺血性卒中的神经保护作用尚未得出一致的结论,其临床疗效似乎并无预期的乐观.因此,有必要对亚低温治疗缺血性卒中由动物实验向临床转化中存在的问题进行分析,为亚低温治疗缺血性卒中的临床应用提供思路.     

大鼠急性缺血性脑损伤后星形胶质细胞的活动及药物对其的影响

目的 探讨大鼠在急性缺血性脑损伤后缺血周边星形胶质细胞(AS)的活动情况和施加药物后对该活动的影响.方法 采用线栓法实施大鼠大脑中动脉阻塞(MCAO)2 h后进行再灌注,制成大鼠脑缺血再灌注模型.然后给予缺血再灌注模型大鼠不同剂量的甘露醇,观察其再灌注后不同时间点的神经功能缺损评分值(mNSS).在缺血再灌注后72 h采用免疫组化法测定各剂量组缺血周边胶质纤维酸性蛋白(GFAP)阳性细胞数目.结果 0剂量组的mNSS和小、中、大剂量组的GFAP阳性细胞数目差别均有统计学意义(P＜0.05),而小、中、大三个不同剂量组的mNSS无统计学差异(P =0.972).不同剂量组缺血周边GFAP阳性细胞数目不完全相同(P =0.009).多重比较结果为:0剂量组分别和小、中、大剂量组比较均P＜0.05,而小、中、大剂量组间检验均P＞0.05.大鼠缺血再灌注后72 h的mNSS和其对应的缺血周边的GFAP阳性细胞数目的Pearson相关系数为-0.828(P =0.005),表明两者间具有负相关性.结论 一定程度上,尚不能认为不同剂量甘露醇对缺血再灌注模型大鼠缺血周边AS的活动影响有区别.模型大鼠的mNSS值和缺血周边的AS数目负相关.本实验证实大鼠急性缺血性脑损伤后,缺血周边AS反应性增生明显.使用甘露醇24 h或72 h后皆可明显增加缺血再灌注模型大鼠缺血周边AS的反应性活动.推断急性缺血性脑损伤后应用甘露醇,可能通过增加缺血周边AS反应性活动对缺血脑组织及周边组织起保护作用.     

脉络宁对新生大鼠缺氧缺血性脑损伤后nNOS和c-Fos表达的影响

目的：检测新生大鼠缺血缺氧后神经元型一氧化氮合酶（nNOS）和c-Fos免疫活性表达改变及脉络宁对其的影响。方法：结扎7d龄大鼠右侧颈总动脉1h，然后暴露在8％氧和92％氮的混合气体中2h，建立缺氧缺血脑损伤模型。用免疫组织化学方法检测并比较缺血缺氧后和脉络宁处理后c-Fos和nNOS的免疫活性。结果：缺血缺氧6h后c-Fos表达达高峰；与缺氧缺血组相比，脉络宁处理组c-Fos阳性神经元数量增加，表达c-Fos的时间延长；与假手术组相比，缺氧缺血组nNOS表达水平增高，脉络宁处理组则下降。结论：脉络宁可抑制nNOS表达，增强c-Fos表达，可能对缺血缺氧性脑损伤有保护作用。     

脑缺血过程中自噬作用的研究进展

缺血性脑卒中是致死致残率极高的一类难治性疾病。越来越多的证据表明,适度的自噬可以清除受损细胞器,从而保护细胞抵御各种伤害;然而,长期过度自噬,使得细胞内容物降解过多引发细胞死亡,导致组织器官严重损伤。在多个不同的缺血性脑损伤动物模型中观察到,缺血性脑损伤过程中自噬被激活并参与其神经元死亡的调节。本文就缺血性脑损伤过程中自噬的相关作用的研究进展做一概述。     

缺血性脑损伤的动物模型及其评价方法

脑缺血的实验研究对于理解缺血性脑损伤的发病机制具有重要的作用,但与临床治疗策略的相关性存在一定的局限性,主要原因之一就是实验动物模型和实验方法 不能或只能部分重复自然脑缺血的病理生理学过程.文章对常用的实验动物模型及其体外和体内评价方法 做了综述.     

Age-dependent cerebral hemodynamic effects of traumatic brain injury in newborn and juvenile pigs

Traumatic brain injury is one of the major causes of morbidity, mortality, and pediatric intensive care unit admissions of children. Although the effects of traumatic brain injury have been well described for adult animal models, few have investigated these effects in the newborn or have characterized such effects as a function of age using a single model of injury. Using a piglet model of brain injury, recent studies have shown that the cerebral hemodynamic effects and the corresponding mechanisms for such effects of injury vary as a functional of age. This review discusses the types of traumatic brain injury, their models, and the role of species in such model choice. This review also describes the effects of brain injury on cerebral blood flow, metabolism, and cerebrovascular regulation as a function of age. Finally, this review presents evidence for potential mechanisms that may contribute to age-dependent impaired cerebral hemodynamics following brain injury.     

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.     

脉络丛上皮细胞在脑缺血中的神经保护作用

脉络丛上皮细胞可分泌多种生物活性肽,包括生长因子和神经营养因子,对促进大脑发育、维持大脑形态和功能稳定具有重要作用.此外,脉络丛上皮细胞具有神经干细胞的特性,将其作为移植细胞治疗脑缺血具有合理性.离体实验和动物实验均证实,脉络丛上皮细胞可通过多种机制抗氧化损伤、减少细胞凋亡和抑制炎性反应,从而发挥神经保护作用.文章对脉络丛上皮细胞在脑缺血中的神经保护作用进行了综述.     

Arterial Hypertension and Brain Damage—Evidence from Animal Models (Review)

Hypertension is an important risk factor for cerebrovascular disease including stroke and has also a role in the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Research on pathophysiology and treatment of hypertensive brain damage may benefit from the availability of animal models. This paper has reviewed the main animal models of hypertension in which brain damage is documented. Spontaneously hypertensive rats (SHR) represent the animal model more largely used. In these rats cerebrovascular changes, brain atrophy, loss of nerve cells in cerebrocortical areas, and glial reaction were documented. Several changes observed in SHR are similar to those found by in vivo imaging studies in essential hypertensives. It is documented that brain gets benefit from lowering abnormally elevated blood pressure and that reduction of hypertension protects brain from stroke and probably reduces the incidence of VaD. The influence of anti‐hypertensive treatment on brain structure and function in animal models of hypertension is reviewed. Among classes of drugs investigated, dihydropyridine‐type Ca²⁺ antagonists were those with a most documented protective effect on hypertensive brain damage. Limits and perspectives in the use of animal models for assessing brain damage caused by hypertension and protection from it are discussed.     

Brain inflammation in neurogenic hypertension

One likely mechanism of essential hypertension (EH) is increased sympathoexcitation due to abnormal functions in the cardiovascular center of the brain. Recent findings obtained using experimental animal models of EH have shown that abnormal inflammation in the cardiovascular center may contribute to the onset of hypertension. Inflammatory molecules such as cytokines and reactive oxygen species released from the inflamed vasculature and glial cells in the medulla oblongata and hypothalamus might directly or indirectly affect neuronal functions. This in turn could increase sympathetic nerve activity and consequently arterial pressure. Abnormal inflammatory responses in the brain could also be central mechanisms underlying angiotensin II-related EH. In this review, we present the current understanding of EH mechanisms with regard to inflammatory responses in the cardiovascular center.     

Sex and steroid hormones in early brain injury

Brain injury during development can have severe, long-term consequences. Using an array of animal models, we have an understanding of the etiology of perinatal brain injury. However, we have only recently begun to address the consequences of endogenous factors such as genetic sex and developmental steroid hormone milieu. Our limited understanding has sometimes led researchers to make over-generalizing and potentially dangerous statements regarding treatment for brain injury. Therefore this review acts as a cautionary tale, speaking to our need to understand the effects of sex and steroid hormone environment on the response to brain trauma in the neonate.     

蛛网膜下腔出血后早期脑损伤

蛛网膜下腔出血(subarachnoid hemorrhage,SAH)是一种致残率和病死率很高的疾病,临床仍缺乏有效的治疗手段.近年来的研究发现,早期脑损伤可能是导致SAH患者病死率较高和决定预后的首要原因.文章主要对SAH早期脑损伤的动物模型和发病机制做了综述.     

Calcium-permeable AMPA/kainate receptors mediate toxicity and preconditioning by oxygen-glucose deprivation in oligodendrocyte precursors

Hypoxic-ischemic brain injury in premature infants results in cerebral white matter lesions with prominent oligodendroglial injury and loss, a disorder termed periventricular leukomalacia (PVL). We have previously shown that glutamate receptors mediate hypoxic-ischemic injury to oligodendroglial precursor cells (OPCs) in a model of PVL in the developing rodent brain. We used primary OPC cultures to examine the mechanism of cellular toxicity induced by oxygen-glucose deprivation (OGD) to simulate brain ischemia. OPCs were more sensitive to OGD-induced toxicity than mature oligodendrocytes, and OPC toxicity was attenuated by nonselective [2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX), 6-cyano-7-nitroquinoxaline-2,3-dione], alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring (GYKI 52466), kainate-preferring (gamma-d-glutamylaminomethanesulfonic acid), or Ca2+-permeable AMPA/kainate receptor antagonists (joro spider toxin, JSTx) administered either during or after OGD. Furthermore, NBQX or JSTx blocked OGD-induced Ca2+ influx. Relevant to recurrent hypoxic-ischemic insults in developing white matter, we examined the effects of sublethal OGD preconditioning. A prior exposure of OPCs to sublethal OGD resulted in enhanced vulnerability to subsequent excitotoxic or OGD-induced injury associated with an increased Ca2+ influx. AMPA/kainate receptor blockade with NBQX or JSTx either during or after sublethal OGD prevented its priming effect. Furthermore, OGD preconditioning resulted in a down-regulation of the AMPA receptor subunit GluR2 on cell surface that increased Ca2+ permeability of the receptors. Overall, these data suggest that aberrantly enhanced activation of Ca2+-permeable AMPA/kainate receptors may be a major mechanism in acute and repeated hypoxic-ischemic injury to OPCs in disorders of developing cerebral white matter, such as PVL.