Regional cerebral blood flow thresholds during cerebral ischemia.

The development of methods of determining regional cerebral blood flow (rCBF) has made possible the determination of thresholds for the appearance of cerebral ischemia. These thresholds vary depending on the method used for assessing cerebral ischemia. The following thresholds have been determined in man and nonhuman primates: 20 cc/100 g per min, electroencephalogram (EEG) and evoked cortical potential abnormalities appear, paralysis seen in waking monkeys; 15 cc/100 g per min. EEG and evoked cortical potential are lost; 12 cc/100 g per min, flows at this level in excess of 120 min produce infarction in waking animals; and 6 cc/100 g per min, massive loss of intracellular [K+]. The residual rCBF and the duration of ischemia determine the appearance of infarction in waking Macaca irus monkeys.     

The cerebral proteopathies

The abnormal assembly and deposition of specific proteins in the brain is the probable cause of most neurodegenerative disease afflicting the elderly. These “cerebral proteopathies” include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), prion diseases, and a variety of other disorders. Evidence is accumulating that the anomalous aggregation of the proteins, and not a loss of protein function, is central to the pathogenesis of these diseases. Thus, therapeutic strategies that reduce the production, accumulation, or polymerization of pathogenic proteins might be applicable to a wide range of some of the most devastating diseases of old age.     

Differential cerebral hypothermia

Differential cerebral hypothermia was induced in these experiments by isolating the cerebral circulation in the halothane-anesthetized goat. The brain was perfused through isolated cerebral branches of the internal maxillary artery using a height-adjusted reservoir system which provided a constant inflow pressure. Cerebral blood flow (CBF) and cerebral O₂ metabolic rate (CMRO₂) were measured continuously as brain temperatures were decreased from 38 to 28, 18 and 8 °C and during rewarming. Arterial blood gases were maintained constant. During hypothermia CBF decreased at brain temperatures of 28 °C and did decrease further at 18 or 8 °C. CMRO₂ decreased linearly from 38 to 8 °C and was 7% control levels at 8 °C. CBF and CMRO₂ returned to control levels upon rewarming. Cerebral lactate metabolism did not change significantly during hypothermia or rewarming. Evoked cortical potentials were abolished at 8 °C but recovered upon rewarming. These results indicate that if adequate brain perfusion is maintained during hypothermia and rewarming, recovery of CBF, metabolism, and brain neural activity can be obtained.     

The role of cerebral oedema in the pathogenesis of cerebral malaria

Abstract

It has been suggested that sequestration of parasitized red blood cells might contribute to the pathogenesis of cerebral malaria (CM), by hypoxia causing either: (i) compensatory vasodilatation with a resultant increase in the brain volume; or (ii) enhancing cytokine-induced nitric oxide (NO) production via induction of inducible NO synthase (iNOS). Available evidence suggests that cerebral oedema is the initiating and probably the most important factor in the pathogenesis of murine CM. The relevance of this model in the study of the pathogenesis of CM has been questioned. However, a closer look at published reports on both human and murine CM, in this review, suggests that the pathogenesis of the murine model of CM might reflect more closely the CM seen in African children than that seen in Asian adults. It is also proposed that the role of iNOS induction during CM is protective: that the primary purpose of iNOS induction is to inhibit the side effects of brain indoleamine 2,3-dioxygenase (IDO) induction and quinolinic acid accumulation during hypoxia.     

The role of cerebral oedema in the pathogenesis of cerebral malaria

It has been suggested that sequestration of parasitized red blood cells might contribute to the pathogenesis of cerebral malaria (CM), by hypoxia causing either: (i) compensatory vasodilatation with a resultant increase in the brain volume; or (ii) enhancing cytokine-induced nitric oxide (NO) production via induction of inducible NO synthase (iNOS). Available evidence suggests that cerebral oedema is the initiating and probably the most important factor in the pathogenesis of murine CM. The relevance of this model in the study of the pathogenesis of CM has been questioned. However, a closer look at published reports on both human and murine CM, in this review, suggests that the pathogenesis of the murine model of CM might reflect more closely the CM seen in African children than that seen in Asian adults. It is also proposed that the role of iNOS induction during CM is protective: that the primary purpose of iNOS induction is to inhibit the side effects of brain indoleamine 2,3-dioxygenase (IDO) induction and quinolinic acid accumulation during hypoxia.     

Changes in cerebral free fatty acids and triacylglycerols in focal cerebral ischemia

1. Focal cerebral ischemia was induced in anesthetized rats by occluding the stem of the proximal middle cerebral artery. 2. The levels of free fatty acids, such as stearic and arachidonic acids, in the ischemic cerebral cortex increased progressively until 60 min after occlusion, but thereafter they decreased rapidly. 3. In contrast to the time-dependent changes in free fatty acids, the levels of triacylglycerol (TAG) in the ischemic cerebral cortex continued to increase for 120 min after occlusion. Increases in TAG-palmitate, -stearate and -arachidonate accounted for the increase in the triacylglycerol level. 4. The pattern of the lipid changes in focal cerebral ischemia differs from those reported in bilateral diffuse cerebral ischemia induced by arterial occlusion or in decapitation ischemia.     

脑出血与脑缺血动物模型脾淋巴细胞的蛋白质组学研究

目的：通过比较正常与脑出血及脑缺血模型大鼠脾淋巴细胞蛋白质表达的差异,初步探讨细胞免疫功能与脑血管病之间的关系。方法：将SD大鼠随机分为正常组、脑出血模型组（采用VII型胶原酶诱导脑出血）和局灶性脑缺血模型组（采用线栓法造成大脑中动脉阻塞）,分离大鼠脾淋巴细胞,提取总蛋白质后进行双向凝胶电泳,考马斯亮蓝染色,PDQUEST软件分析,对差异蛋白质点采用基质辅助激光解析电离质谱（MALDI-TOF-MS）技术进行鉴定并分析。结果：胶质细胞成熟因子 等9个蛋白在脑出血和脑缺血模型组表达上调,膜联蛋白III在脑出血和脑缺血模型组表达下调。结论：建立了分辨率高重复性较好的脑出血及局灶性脑缺血脾淋巴细胞总蛋白的双向凝胶电泳图谱,并鉴定一些与脑血管病脑损伤相关的差异表达蛋白质,为深入研究脑血管病细胞免疫功能改变与脑血管病之间的关系奠定了基础。     

Immunopathogenesis of cerebral malaria

Malaria is one of the most important global health problems, potentially affecting more than one third of the world's population. Cerebral malaria (CM) is a deadly complication of Plasmodium falciparum infection, yet its pathogenesis remains incompletely understood. In this review, we discuss some of the principal pathogenic events that have been described in murine models of the disease and relate them to the human condition. One of the earliest events in CM pathogenesis appears to be a mild increase in the permeability to protein of the blood-brain barrier. Recent studies have shown a role for CD8+T cells in mediating damage to the microvascular endothelium and this damage can result in the leakage of cytokines, malaria antigens and other potentially harmful molecules across the blood-brain barrier into the cerebral parenchyma. We suggest that this, in turn, leads to the activation of microglia and the activation and apoptosis of astrocytes. The role of hypoxia in the pathogenesis of cerebral malaria is also discussed, with particular reference to the local reduction of oxygen consumption in the brain as a consequence of vascular obstruction, to cytokine-driven changes in glucose metabolism, and to cytopathic hypoxia. Interferon-gamma, a cytokine known to be produced in malaria infection, induces increased expression, by microvascular endothelial cells, of the haem enzyme indoleamine 2,3-dioxygenase, the first enzyme in the kynurenine pathway of tryptophan metabolism. Enhanced indoleamine 2,3-dioxygenase expression leads to increased production of a range of biologically active metabolites that may be part of a tissue protective response. Damage to astrocytes may result in reduced production of the neuroprotectant molecule kynurenic acid, leading to a decrease in its ratio relative to the neuroexcitotoxic molecule quinolinic acid, which might contribute to some of the neurological symptoms of cerebral malaria. Lastly, we discuss the role of other haem enzymes, cyclooxygenase-2, inducible nitric oxide synthase and haem oxygenase-1, as potentially being components of mechanisms that protect host tissue against the effects of cytokine- and leukocyte-mediated stress induced by malaria infection.