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

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.

• Authors: Xiaoyan Ren, Hong Ma, Zhiyi Zuo
• Journal: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology (J Neuroimmune Pharmacol) Vol. 11 Issue 2 Pg. 238-47 (06 2016) ISSN: 1557-1904 [Electronic] United States
• PMID: 26932203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Neuroprotective Agents
• Dexmedetomidine

Topics

• Adrenergic alpha-2 Receptor Agonists (pharmacology, therapeutic use)
• Animals
• Animals, Newborn
• Brain Injuries (metabolism, pathology, prevention & control)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Dexmedetomidine (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Hypoxia-Ischemia, Brain (drug therapy, metabolism, pathology)
• Ischemic Postconditioning (methods)
• Maze Learning (drug effects, physiology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley