Activation of acetylcholine receptors and microglia in hypoxic-ischemic brain damage in newborn rats

Abstract

Objective: We previously showed that acetylcholine receptor (AChR) agonist reduced hypoxic-ischemic brain damage in the newborn rats. To further investigated the interaction between hypoxia and chorinergic anti-inflammatory pathway, we examined the effect of AChR antagonist on brain damage and to see the relation between microglial activation and protective effect of AChR agonist. Study design: Seven-day-old Wistar rats were divided into 2 groups, one receiving AChR antagonists to see if they have deleterious effects on hypoxic-ischemic brain damage, and the other receiving AChR agonist, carbachol, to investigate the emergence of microglia in the hippocampus. Rats were subjected to left carotid artery ligation followed by 8% hypoxia. Brains were analyzed histologically and immunohistochemically. Results: Antagonists of AChRs significantly enhanced brain damage in 1-h hypoxia-ischemia. In particular, the nicotinic AChR antagonist showed a marked enhancement of brain damage compared to the saline controls (p<0.01). The hippocampal CA1 was most vulnerable to any AChR antagonists, while the cortex was least vulnerable and only responsive to a higher dose of non-selective nAChR antagonist. Carbachol showed significantly less accumulation of microglia in the hippocampus than the saline controls (p<0.01) in hypoxia–ischemia. Conclusion: An AchR-responsive pathway in the brain plays an important role in modifying perinatal brain damage, in which microglial accumulation may be involved.