Inflammatory mechanisms in ischemic stroke: therapeutic approaches

被引:871
作者
Lakhan, Shaheen E. [1 ]
Kirchgessner, Annette [1 ]
Hofer, Magdalena [1 ]
机构
[1] Global Neurosci Initiat Fdn, Los Angeles, CA USA
关键词
MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; FOCAL CEREBRAL-ISCHEMIA; REGULATORY T-CELLS; ISCHEMIA/REPERFUSION INJURY; OXIDATIVE STRESS; OXYGEN-THERAPY; EXPRESSION; ANTIOXIDANT; REPERFUSION;
D O I
10.1186/1479-5876-7-97
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies.
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页数:11
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