Microcirculatory disturbances in cerebral ischemia; Analysis of pathophysiology and therapeutic approach

1.局灶性脑缺血微循环障碍的病理过程我们以前的研究表明，大鼠局灶性脑缺血数小时内，缺血灶内的血浆微血管长度减少。本研究的目的是阐明这种微循环障碍的机制.超氧化物歧化酶（SOD）的作用：在急性局灶性脑缺血的几小时内连续给予SOD，微血管的通畅性得到了显著的保护。提示脑缺血急性期超氧化物的形成可能导致内皮细胞损伤，促进血管内血栓形成。SOD的应用也减少了组织学上明显的损伤的大小.通过微循环保护缺血性脑损伤本研究表明SOD可能是一种有效的脑缺血保护剂。虽然SOD被认为可以通过清除导致组织损伤的自由基直接减轻组织损伤，但本研究表明，SOD对微循环的保护也可能有助于保护脑损伤免受脑缺血。由于重组人SOD可用于心脏病发作的临床试验，因此也期望使用该药剂来对抗脑缺血。

1. Pathologic process of microcirculatory disturbance in focal cerebral ischemia.Our previous study demonstrated that the length of plasma-per fused microvessels decreased in the ischemic foci during the several hours of rat focal cerebral ischemia. The aim of the present investigation is to elucidate the mechanism of this microcirculatory disturbance.2. Effect of superoxide dismutase (SOD).When SOD was administered continuously during the several hours of acute focal cerebral ischemia, the microvascular patency was significantly preserved. Those data suggests that the formation superoxide during the acute stage of cerebral ischemia may cause endothelial injury and facilitate intravascular clot formation. The application of SOD also decreased the size of histologically noticeable damage.3. Protection of ischemic brain damage via preservation of microcirculation.The present study demonstrated SOD could be a useful agent to protect the brain against ischemia. Although SOD has been expected to reduce tissue damage directly by eliminating free radicals that cause tissue injury, the present study suggested preservation of microcirculation by SOD may also contribute to protect brain injury against cerebral ischemia. Since recombinant human SOD is available for clinical trial for cardiac attacks, the use of this agent against cerebral ischemia is also expected.