Ischemic brain injury such as stroke is a leading cause of neurological disability and death in the States. There is, however, no effective strategy to protect the brain from ischemic injury. Recently, we have made exciting observations on effect of electro-acupuncture (EA) on cerebral ischemia. The most striking finding is that EA remarkably reduces brain infarction due to the occlusion of middle cerebral artery, which is dependent on the EA-triggered cellular/molecular events in the brain. Since our studies and those of others have shown that 1) activation of delta-opioid receptor (DOR) attenuates hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal apoptosis and death;2) DOR up-regulation enhances intracellular survival signals;3) opioid receptor activation inhibits inflammatory responses, e.g., production of inflammatory cytokines that plays a critical role in ischemic injury;and 4) DOR inhibition largely attenuates the EA-induced protection against ischemic injury, it is likely that the EA-induced protection represents the outcome of cellular and molecular regulation at multiple levels in the brain. Specifically, it may depend on DOR up-regulation and the DOR-mediated stabilization of ionic homeostasis and modulation of survival/death signals. The general hypothesis of this proposal is that EA protects against cerebral ischemia mainly through DOR up-regulation and the DOR-mediated modulation of cellular and molecular signaling in neurons.. With molecular, transgenic and electrophysiological approaches, this proposal is designed to accomplish 3 specific aims: 1) to investigate if EA protects the brain from cerebral ischemia via DOR up-regulation;2) to investigate if the EA protection is mediated by DOR-based stabilization of ionic homeostasis;and 3) to investigate if the EA protection relies on DOR-mediated inhibition of inflammatory responses to ischemia. The outcome data of this project may yield important information on the mechanism underlying the EA-induced protection from cerebral ischemia and may provide novel clues for therapeutic solutions of stroke.

Public Health Relevance

Stroke is a leading cause of neurological disability and death in the United States. However, there is no effective therapy to date to protect the brain from stroke-induced brain injury. To seek novel approaches to prevent/treat stroke, we have recently made exciting observations on the effect of electro- acupuncture (EA) on stroke-induced injury. The most striking and surprising finding is that EA, through little needles without any other treatment, remarkably reduces stroke-induced brain injury via the regulation of delta-opioid receptor (a cell membrane protein). Also, functional studies showed that EA promotes the recovery of brain function after stroke. Our finding thus suggests important therapeutic potential for EA in stroke. In this application, we propose to use modern techniques including molecular, transgenic and electrophysiological approaches to test three specific hypotheses for exploring mechanisms underlying the EA protection against stroke. Our preliminary studies have shown that this proposal is feasible and will very likely yield important information on the EA-induced protection and eventually shed light on new therapeutic modalities of stroke.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Project (R01)
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Clinical Neuroscience and Disease Study Section (CND)
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Huntley, Kristen V
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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Wang, Qinyu; Chao, Dongman; Chen, Tao et al. (2014) ?-Opioid receptors and inflammatory cytokines in hypoxia: differential regulation between glial and neuron-like cells. Transl Stroke Res 5:476-83
Fenoy, Albert J; Goetz, Laurent; Chabardès, Stéphan et al. (2014) Deep brain stimulation: are astrocytes a key driver behind the scene? CNS Neurosci Ther 20:191-201
Chen, Fan; Qi, Zhifeng; Luo, Yuming et al. (2014) Non-pharmaceutical therapies for stroke: mechanisms and clinical implications. Prog Neurobiol 115:246-69
Chen, Tao; Li, Jessica; Chao, Dongman et al. (2014) ?-Opioid receptor activation reduces ?-synuclein overexpression and oligomer formation induced by MPP(+) and/or hypoxia. Exp Neurol 255:127-36
Tian, Xuesong; Guo, Jingchun; Zhu, Min et al. (2013) ýý-Opioid receptor activation rescues the functional TrkB receptor and protects the brain from ischemia-reperfusion injury in the rat. PLoS One 8:e69252
He, Xiaozhou; Sandhu, Harleen K; Yang, Yilin et al. (2013) Neuroprotection against hypoxia/ischemia: ýý-opioid receptor-mediated cellular/molecular events. Cell Mol Life Sci 70:2291-303
Cao, Jian; Wang, Suhong; Ren, Yanling et al. (2013) Interference control in 6-11 year-old children with and without ADHD: behavioral and ERP study. Int J Dev Neurosci 31:342-9
He, Xiaozhou; Yang, Yilin; Zhi, Feng et al. (2013) ýý-Opioid receptor activation modified microRNA expression in the rat kidney under prolonged hypoxia. PLoS One 8:e61080
Tian, Xuesong; Hua, Fei; Sandhu, Harleen K et al. (2013) Effect of ýý-opioid receptor activation on BDNF-TrkB vs. TNF-* in the mouse cortex exposed to prolonged hypoxia. Int J Mol Sci 14:15959-76
Xu, Yunqi; Yan, Junqiang; Zhou, Peng et al. (2012) Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease. Prog Neurobiol 97:1-13

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