Neuroprotection targeting ischemic penumbra and beyond for the treatment of ischemic stroke

被引:51
作者
Liu, Ran [1 ,2 ]
Yuan, Hui [3 ]
Yuan, Fang [3 ]
Yang, Shao-Hua [1 ,2 ]
机构
[1] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol, Ft Worth, TX 76107 USA
[2] Univ N Texas, Hlth Sci Ctr, Dept Neurosci, Ft Worth, TX 76107 USA
[3] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China
基金
美国国家卫生研究院;
关键词
Stroke; Ischemia; Neuroprotection; Penumbra; MIDDLE CEREBRAL-ARTERY; NEURAL STEM/PROGENITOR CELLS; ACTIVATED PROTEIN-KINASE; QUANTITATIVE DIFFUSION; BEHAVIORAL RECOVERY; POSTSTROKE DEMENTIA; THRESHOLD DURATION; ADULT BRAIN; TISSUE FATE; STEM-CELLS;
D O I
10.1179/1743132812Y.0000000020
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:331 / 337
页数:7
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