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Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats

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Abstract

Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7 days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1 h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28 days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues.

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Abbreviations

α2AR:

α2-adrenergic receptors

DMSO:

dimethyl sulfoxide

HI:

hypoxia-ischemia

IL-1β:

interleukin-1β

TNFα:

tumor necrosis factor α

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Authors and Affiliations

  1. Department of Anesthesiology, University of Virginia, Charlottesville, VA, 22908, USA

    Xiaoyan Ren & Zhiyi Zuo

  2. Department of Anesthesiology, First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China

    Xiaoyan Ren & Hong Ma

Authors
  1. Xiaoyan Ren
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  2. Hong Ma
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  3. Zhiyi Zuo
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Correspondence to Hong Ma or Zhiyi Zuo.

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Grant Support

This study was supported by a grant (R01 GM098308 to Z Zuo) from the National Institutes of Health, Bethesda, MD, by a grant from the International Anesthesia Research Society (2007 Frontiers in Anesthesia Research Award to Z Zuo), Cleveland, OH, by a Grant-in-Aid from the American Heart Association Mid-Atlantic Affiliate (10GRNT3900019 to Z Zuo), Baltimore, MD, and the Robert M. Epstein Professorship endowment, University of Virginia, Charlottesville, VA.

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The authors declare no competing financial interests.

Additional information

The research was performed in the Department of Anesthesiology, University of Virginia.

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Ren, X., Ma, H. & Zuo, Z. Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats. J Neuroimmune Pharmacol 11, 238–247 (2016). https://doi.org/10.1007/s11481-016-9658-9

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