Departments of Neurology, Neurosciences, Cell Biology and Physiology and Mathematics and Statistics, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
J Cereb Blood Flow Metab. 2012 Jul;32(7):1139-51. doi: 10.1038/jcbfm.2011.197. Epub 2012 Jan 18.
Disruption of the blood-brain barrier (BBB) has an important part in cellular damage in neurological diseases, including acute and chronic cerebral ischemia, brain trauma, multiple sclerosis, brain tumors, and brain infections. The neurovascular unit (NVU) forms the interface between the blood and brain tissues. During an injury, the cascade of molecular events ends in the final common pathway for BBB disruption by free radicals and proteases, which attack membranes and degrade the tight junction proteins in endothelial cells. Free radicals of oxygen and nitrogen and the proteases, matrix metalloproteinases and cyclooxgyenases, are important in the early and delayed BBB disruption as the neuroinflammatory response progresses. Opening of the BBB occurs in neurodegenerative diseases and contributes to the cognitive changes. In addition to the importance of the NVU in acute injury, angiogenesis contributes to the recovery process. The challenges to treatment of the brain diseases involve not only facilitating drug entry into the brain, but also understanding the timing of the molecular cascades to block the early NVU injury without interfering with recovery. This review will describe the molecular and cellular events associated with NVU disruption and potential strategies directed toward restoring its integrity.
血脑屏障（BBB）的破坏在包括急性和慢性脑缺血、脑创伤、多发性硬化、脑肿瘤和脑部感染在内的神经疾病的细胞损伤中起着重要作用。神经血管单元（NVU）形成了血液和脑组织之间的界面。在损伤过程中，分子事件级联反应最终通过自由基和蛋白酶导致 BBB 破坏的共同途径，这些自由基和蛋白酶攻击膜并降解内皮细胞中的紧密连接蛋白。氧和氮自由基以及蛋白酶、基质金属蛋白酶和环氧化酶在神经炎症反应进展时，在早期和迟发性 BBB 破坏中非常重要。BBB 的开放发生在神经退行性疾病中，并导致认知变化。除了 NVU 在急性损伤中的重要性之外，血管生成有助于恢复过程。脑部疾病治疗的挑战不仅包括促进药物进入大脑，还包括了解分子级联反应的时机，以阻止早期 NVU 损伤而不干扰恢复。本综述将描述与 NVU 破坏相关的分子和细胞事件，并介绍针对恢复其完整性的潜在策略。
