The selective alpha7 nicotinic acetylcholine receptor agonist AR-R17779 does not affect ischemia-reperfusion brain injury in mice

Inflammation plays a central role in stroke-induced brain injury. The alpha7 nicotinic acetylcholine receptor (alpha 7nAChR) can modulate immune responses in both the periphery and the brain. The aims of the present study were to investigate alpha 7nAChR expression in different brain regions and evaluate the potential effect of the selective alpha 7nAChR agonist AR-R17779 on ischemia-reperfusion brain injury in mice. Droplet digital PCR (ddPCR) was used to evaluate the absolute expression of the gene encoding alpha 7nAChR (Chrna7) in hippocampus, striatum, thalamus and cortex in adult, naive mice. Mice subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery were treated with alpha 7nAChR agonist AR-R17779 (12 mg/kg) or saline once daily for 5 days. Infarct size and microglial activation 7 days after tMCAO were analyzed using immunohistochemistry. Chrna7 expression was found in all analyzed brain regions in naive mice with the highest expression in cortex and hippocampus. At sacrifice, white blood cell count was significantly decreased in AR-R17779 treated mice compared with saline controls in the sham groups, although, no effect was seen in the tMCAO groups. Brain injury and microglial activation were evident 7 days after tMCAO. However, no difference was found between mice treated with saline or AR-R17779. In conclusion, alpha 7nAChR expression varies in different brain regions and, despite a decrease in white blood cells in sham mice receiving AR-R17779, this compound does not affect stroke-induced brain injury.

Automated summary

The study investigated the expression of alpha 7nAChR in different brain regions and evaluated the potential effect of the alpha 7nAChR agonist AR-R17779 on ischemia-reperfusion brain injury in mice. It was found that alpha 7nAChR expression varies in different brain regions, and despite a decrease in white blood cells in sham mice receiving AR-R17779, this compound does not affect stroke-induced brain injury.