Liu Ran, Yuan Hui, Yuan Fang, Yang Shao-Hua
Departments of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
Neurol Res. 2012 May;34(4):331-7. doi: 10.1179/1743132812Y.0000000020.
Neuroprotection to attenuate or block the ischemic cascade and salvage neuronal damage has been extensively explored for the treatment of ischemic stroke. In the last two decades, neuroprotective strategy has been evolving from targeting a signal pathway in neurons to protecting all neurovascular components and improving cell-cell and cell-extracellular matrix interaction that ultimately benefits the brain recovery after ischemic stroke. The progression from potentially reversible to irreversible injury in the ischemic penumbra has provided the opportunity to develop therapies to attenuate the ischemic stroke damage. Thus, the ischemic penumbra has been the main target for the current neuroprotective intervention. However, despite our increasing knowledge of the physiologic, mechanistic, and imaging characterizations of the ischemic penumbra, no effective neuroprotective therapy has been found so far for the treatment of ischemic stroke. The current acute neuroprotective approach focusing on the damaging mechanisms at the ischemic penumbra is greatly limited by the rapid evolution of the deleterious cascades in the ischemic penumbra. Neuroprotective intervention attempts to promote endogenous repairing in the transition zone of the penumbra for the therapeutic purposes may overcome the unrealistic therapeutic windows under the current neuroprotective strategy. In addition, increasing evidence has indicated ischemic stroke could induce long-lasing cellular and hemodynamic changes beyond the ischemic territory. It is unclear whether and how the global responses induced by the ischemic cascade contribute to the progression of cognitive impairment after ischemic stroke. The prolonged pathophysiological cascades induced by ischemic stroke beyond the ischemic penumbra might provide novel therapeutic opportunities for the neuroprotective intervention, which could prevent or slow down the progression of vascular dementia after ischemic stroke.
为了治疗缺血性中风，人们广泛探索了神经保护作用，以减轻或阻断缺血级联反应并挽救神经元损伤。在过去的二十年中，神经保护策略已从针对神经元中的信号通路发展到保护所有神经血管成分，并改善细胞间和细胞与细胞外基质的相互作用，这最终有利于缺血性中风后的大脑恢复。缺血半暗带中从潜在可逆性损伤到不可逆性损伤的进展为开发减轻缺血性中风损伤的疗法提供了机会。因此，缺血半暗带一直是当前神经保护干预的主要靶点。然而，尽管我们对缺血半暗带的生理、机制和影像学特征的了解不断增加，但迄今为止尚未发现有效的神经保护疗法来治疗缺血性中风。目前专注于缺血半暗带损伤机制的急性神经保护方法受到缺血半暗带中有害级联反应快速演变的极大限制。为了治疗目的，在半暗带的过渡区促进内源性修复的神经保护干预尝试可能会克服当前神经保护策略下不切实际的治疗窗口。此外，越来越多的证据表明，缺血性中风可在缺血区域之外诱发长期的细胞和血流动力学变化。目前尚不清楚缺血级联反应引发的整体反应是否以及如何导致缺血性中风后认知障碍的进展。缺血性中风在缺血半暗带之外引发的长时间病理生理级联反应可能为神经保护干预提供新的治疗机会，从而预防或减缓缺血性中风后血管性痴呆的进展。
