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A novel insight into neuroprotection against hypoxic/ischemic stress

FENG Yuan, CHAO Dongman, HE Xiaozhou, YANG Yilin, KANG Xuezhi, Lawrence H LAZARUS, XIA Ying

Yale University School of Medicine, New Haven, CT 06520, USA； TheFirst Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China； The Third Clinical College of Soochow University, Changzhou 213003, China； Shanghai Research Center for Acupuncture and Meridians, Shanghai 201203, China； National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Abstract

The use of opioid analgesics has a long history in clinical settings, although the functions of opioid receptors, especially their role in the brain, are not well understood yet. Recent studies have generated abundant new data on opioid receptor-mediated functions and the underlying mechanisms. The most exciting finding in the past decade is probably the neuroprotection against hypoxic/ischemic stress mediated by δ-opioid receptors (DOR). An up-regulation of DOR expression and the release of endogenous opioids may increase neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers, depending on stress duration and severity, different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of ionic homeostasis, an increase in pro-survival signaling (e.g., PKC-ERK-Bcl 2) and the enhanced anti-oxidative capacity. Recent data on DOR-mediated neuroprotection provide us a new concept of neuroprotection against neurological disorders and have a potentially significant impact on the prevention and treatment of some serious neurological conditions, such as stroke.

Key words: opioids; δ-opioid receptors; neurotransmitters; brain, ionic homeostasis; neuroprotection; hypoxia; ischemia;

Received: 2009-11-30　　Accepted: 2009-12-16

Corresponding author: 夏萤　　E-mail: ying.xia@yale.edu

Citing This Article：

FENG Yuan, CHAO Dongman, HE Xiaozhou, YANG Yilin, KANG Xuezhi, Lawrence H LAZARUS, XIA Ying. A novel insight into neuroprotection against hypoxic/ischemic stress. Acta Physiol Sin 2009; 61 (6): 585-592 (in Chinese with English abstract).