Department of Neurology, University of New Mexico, Albuquerque, NM 87107, USA.
Stroke. 2011 Nov;42(11):3323-8. doi: 10.1161/STROKEAHA.110.608257. Epub 2011 Sep 22.
Disruptions of the blood-brain barrier (BBB) and edema formation both play key roles in the development of neurological dysfunction in acute and chronic cerebral ischemia. Animal studies have revealed the molecular cascades that are initiated with hypoxia/ischemia in the cells forming the neurovascular unit and that contribute to cell death. Matrix metalloproteinases cause reversible degradation of tight junction proteins early after the onset of ischemia, and a delayed secondary opening during a neuroinflammatory response occurring from 24 to 72 hours after. Cyclooxygenases are important in the delayed opening as the neuroinflammatory response progresses. An early opening of the BBB within the 3-hour therapeutic window for tissue-type plasminogen activator can allow it to enter the brain and increase the risk of hemorrhage. Chronic hypoxic hypoperfusion opens the BBB, which contributes to the cognitive changes seen with lacunar strokes and white matter injury in subcortical ischemic vascular disease. This review will describe the molecular and cellular events associated with BBB disruption and potential therapies directed toward restoring the integrity of the neurovascular unit.
血脑屏障（BBB）的破坏和水肿的形成在急性和慢性脑缺血引起的神经功能障碍的发展中都起着关键作用。动物研究揭示了在形成神经血管单元的细胞中缺氧/缺血引发的分子级联反应，这些反应导致细胞死亡。基质金属蛋白酶在缺血发生后早期可逆地降解紧密连接蛋白，而在缺血后 24 至 72 小时发生的神经炎症反应期间发生延迟的继发性开放。环氧化酶在神经炎症反应进展过程中对于延迟性开放很重要。组织型纤溶酶原激活物的 3 小时治疗窗内 BBB 的早期开放可使其进入大脑，并增加出血的风险。慢性缺氧低灌注会打开 BBB，这导致腔隙性卒中以及皮质下缺血性血管疾病中的白质损伤中出现认知变化。这篇综述将描述与 BBB 破坏相关的分子和细胞事件，以及针对恢复神经血管单元完整性的潜在治疗方法。
