Review

Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury

Authors: Xing-miao Chen, Han-sen Chen, Ming-jing Xu, Jian-gang Shen
DOI: 10.1038/aps.2012.82

Abstract

Xing-miao CHEN, Han-sen CHEN, Ming-jing XU, Jian-gang SHEN*

School of Chinese Medicine, Research Centre of Heart, Brain, Hormone & Healthy Aging, The University of Hong Kong, Hong Kong SAR, China

Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO–), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO–) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO– to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.


Keywords: stroke; cerebral ischemia-reperfusion injury; reactive nitrogen species; nitric oxide; peroxynitrite; drug discovery

This work was supported by Hong Kong RGC General Research Fund (GRF No 774808M, 777610M, 777611M) and Seed Funding Programme for Basic Research at the University of Hong Kong (201011159053).
* To whom correspondence should be addressed.
E-mail shenjg@hkucc.hku.hk
Received 2012-04-01 Accepted 2012-05-22
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