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Neuroprotection against hypoxia/ischemia: δ-opioid receptor-mediated cellular/molecular events

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Abstract

Hypoxic/ischemic injury remains the most dreaded cause of neurological disability and mortality. Despite the humbling experiences due to lack of promising therapy, our understanding of the complex cascades underlying the neuronal insult has led to advances in basic science research. One of the most noteworthy has been the effect of opioid receptors, especially the delta-opioid receptor (DOR), on hypoxic/ischemic neurons. Our recent studies, and those of others worldwide, present strong evidence that sheds light on DOR-mediated neuroprotection in the brain, especially in the cortex. The mechanisms of DOR neuroprotection are broadly categorized as: (1) stabilization of the ionic homeostasis, (2) inhibition of excitatory transmitter release, (3) attenuation of disrupted neuronal transmission, (4) increase in antioxidant capacity, (5) regulation of intracellular pathways—inhibition of apoptotic signals and activation of pro-survival signaling, (6) regulation of specific gene and protein expression, and (7) up-regulation of endogenous opioid release and/or DOR expression. Depending upon the severity and duration of hypoxic/ischemic insult, the release of endogenous opioids and DOR expression are regulated in response to the stress, and DOR signaling acts at multiple levels to confer neuronal tolerance to harmful insult. The phenomenon of DOR neuroprotection offers a potential clue for a promising target that may have significant clinical implications in our quest for neurotherapeutics.

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Acknowledgments

This work was supported by grants of NIH (HD-034852, AT-004422), Vivian L. Smith Neurologic Foundation, NSFC (31071046), CSDP (CS20102010) and CHB (ZD201007).

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Authors and Affiliations

  1. The Third Clinical College of Suzhou University, Changzhou, Jiangsu, China

    Xiaozhou He, Yilin Yang & Fei Hua

  2. The Vivian L Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, 77030, TX, USA

    Harleen K. Sandhu, Nathalee Belser, Dong H. Kim & Ying Xia

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  1. Xiaozhou He
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  2. Harleen K. Sandhu
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Correspondence to Ying Xia.

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Xiaozhou He and Harleen K. Sandhu contributed equally.

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He, X., Sandhu, H.K., Yang, Y. et al. Neuroprotection against hypoxia/ischemia: δ-opioid receptor-mediated cellular/molecular events. Cell. Mol. Life Sci. 70, 2291–2303 (2013). https://doi.org/10.1007/s00018-012-1167-2

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