Ethanol and brain damage

It is now well established that even uncomplicated alcoholics who have no specific neurological or hepatic problems show signs of regional brain damage and cognitive dysfunction. Improvements in neuroimaging technology, magnetic resonance imaging, magnetic resonance spectroscopy and positron emission tomography have contributed significantly, revealing alcoholic-specific changes in the CNS associated with neuropsychological abnormalities. Although greater efforts are needed, a human brain bank specifically targeting alcohol cases is now able to provide fresh and frozen tissue for alcohol researchers. These tissues can be used to test hypotheses developed using animal models and/or in vitro studies. The aim is to delineate mechanisms underlying alcohol-related brain damage in humans. The development of high-throughput, non-hypothesis-driven approaches using DNA microarrays and proteomics might also provide clues to this important problem.     

Alcohol and brain damage

The effect of alcohol upon the brain has been studied, ranging from a consumption of 10 g/day to the level of the acknowledged alcoholic (120 g/day or more). In the first instance the CT results of social drinkers and alcoholics were compared with the findings in a group of normal volunteers. Subsequently a group of light to moderate drinkers were examined to investigate the reationship between CT findings, psycho-metric results and alcohol intake. A study of haematological and biochemical parameters of nutrition and liver function was undertaken and these findings were matched with the dietary history recorded for a one-week period by the volunteers. The local results were compared with those of other workers. 26 subjects out of a total of 65 light to moderate drinkers agreed to abstain from alcohol for a period of 6 months and the tests were all repeated. Improvements were found in total CT atrophy, psychometric results and biochemistry. Work-in-progress is the recall of all subjects, irrespective of whether or not they have returned to social drinking. Those subjects who only had an initial examination are also being recalled to establish the progress if any, of the originally demonstrated brain damage, as a result of continued drinking.     

Mechanisms of ischemic brain damage

In the United States stroke is the third leading cause of death and the leading cause of disability. Brain injury following stroke results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation and apoptosis. There are very few treatments for stroke and the development of new treatments requires a comprehensive understanding of the diverse mechanisms of ischemic brain damage that are responsible for neuronal death. Here, we discuss the underlying pathophysiology of this devastating disease and reveal the intertwined pathways that are the target of therapeutic intervention.     

GMP-140与缺血性脑损伤

血小板是血液循环内最小的无核细胞成分,具有丰富的胞内颗粒,当受到物理或生理刺激因子作用时,血小板发生活化,伸出伪足并释放胞内颗粒内容物,参与生理性止血和病理性血栓形成。GMP-140是血小板活化依赖的颗粒膜外显蛋白(PADGEM)犤1犦,在缺血损伤病理过程中的作用越来越引起人们的重视。现就几年来GMP-140的生物学研究进展及在缺血性脑损伤病理过程中的作用综述如下。1GMP-140结构特点GMP-140是一个富含半胱氨酸,高度糖化的整合蛋白质,分子骨架由一条多肽链构成,SPS-PAGE分析示GMP-140的分子量为14万kD,还原后分子量不变犤2犦。…     

Fetal alcohol syndrome and brain damage

Alcohol exposure in utero causes mental retardation in humans. This paper reviews animal studies of alcohol exposure during both pre-natal and early post-natal periods demonstrating that alcohol disrupts the structural development of the central nervous system. More specifically, the proliferation of neurons has been delayed. Migration patterns are altered in the cerebral cortex where neuronal precursors remain in the deep layers rather than continuing into the more superficial layers. Differentiation of dendritic arborization appears to be suppressed in pyramidal neurons in the cortex and hippocampus and aberrant synaptic connectivity can be observed. The distribution and shape of dendritic spines appear immature at some time periods, although these alterations may recover by adulthood. The changes in the development of the central nervous system are reflected in behavioural dysfunction.     

重型颅脑外伤后二次脑损伤相关因素临床观察

目的：探讨引起重型颅脑外伤二次脑损伤的相关因素。方法：回顾性分析2004年6月～2009年6月本科治疗的重型颅脑损伤168例患者的临床资料;比较死亡组与存活组的WBC计数、体温、血压、血糖、血钠水平差异。结果：168例患者死亡49例（29.17%）;两组比较死亡组WBC计数、体温、血糖、血钠水平高,血压低。结论：影响重型颅脑损伤预后二次损伤因素较多,应高度重视监测和严格控制二次脑损伤相关因素。     

亚低温治疗新生兔缺氧缺血性脑损伤脑温监测的研究

目的探讨缺氧缺血性脑损伤（HIBD）新生兔头皮温度与颅内温度之间的关系。方法选择HIBD模型动物12只，作为探针动物。将探针动物置于亚低温治疗仪内，在降温过程中，监测从初始温度（35℃）开始降温达到不同颅内温度的时间和相应的头皮温度，并进行分析。结果颅内温度从35℃降至28℃所需的平均时间为37．5min，头颅温度与头皮温度呈良好的直线正相关关系（r=0．934，P〈0．05）。结论在一定的温度范围内，实验动物头皮温度与颅内温度有较强的直线正相关关系，可通过对头皮温度的测定，间接推断动物的颅内温度。     

核黄素抑制大鼠缺血性脑损伤

目的探讨核黄素对缺血性脑损伤的保护作用及其机制。方法在体实验,采用SD♂大鼠,随机分为对照组、模型组和核黄素组。核黄素组大鼠腹腔注射核黄素1 mg·kg~(-1),连续7 d后,模型组和核黄素组大鼠用线栓法制作大脑中动脉栓死(middle cerebral artery occlusion,MCAO)模型。术后24 h,用2,3,5-氯化三苯基四氮唑(triphenyl tetrazolium chloride,TTC)检测脑梗死面积、称重法检测脑水肿状况、电镜观察缺血处脑皮层超微结构变化。离体实验采用原代培养的大鼠脑皮层神经元制备氧糖剥夺(oxygen and glycose deprivation,OGD)模型。用噻唑蓝[3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide,MTT]法检测OGD后神经元活力、电镜观察神经元超微结构变化。大鼠经MCAO模型24 h后,对脑组织中的超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的酶活力进行测定。结果核黄素明显减少MCAO引起的脑梗死面积(P<0.01)、抑制脑水肿(P<0.01)、抑制亚细胞结构损伤;核黄素明显保护神经元OGD后的细胞活力(P<0.01)和亚细胞结构。核黄素明显提高铜锌SOD(Cu-Zn SOD,SOD1)、GSH-Px和CAT的酶活力(P<0.01);而对锰SOD(Mn-SOD,SOD2)的酶活力无影响。结论核黄素对大鼠缺血性脑损伤具有保护作用,其作用机制包括保护缺血时脑组织的抗氧化酶活力。     

Felbamate reduces hypoxic-ischemic brain damage in vivo.

The neuroprotective effects of felbamate were tested in a model of incomplete cerebral ischemia and hypoxia in 7-day-old rat pups. Felbamate pretreatment (300 mg/kg) reduced the surface of infarcted cortex following bilateral carotid ligation, by 42-49% compared to saline and dimethylsulfoxide (DMSO) controls, respectively. The number of necrotic neurons in the dentate gyrus was reduced by 77% over both DMSO controls and saline controls. These results suggest that felbamate deserves further evaluation for its therapeutic potential in hypoxia-ischemia.