Expression and distribution of pituitary adenylate cyclase-activating polypeptide receptor in reactive astrocytes induced by global brain ischemia in mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neuroprotectant. We previously showed that PACAP receptor (PAC1R) immunoreactivity was elevated in reactive astrocytes after stab wound injury. However, the pattern of PAC1R expression in astrocytes after brain injury is still unknown. In this study, PAC1R expression was evaluated in mouse hippocampal astrocytes after bilateral common carotid artery occlusion. PAC1R mRNA levels in the hippocampus peaked on day 7, and glial fibrillary acidic protein (GFAP) mRNA levels increased from day 3 to day 7 after ischemia. We then observed co-localization of PAC1R and GFAP by double immunostaining. GFAP-immunopositive cells showed signs of hypertrophy 3 days after the ischemia, and by day 7 had fine processes, were hypertrophied, and are known as reactive astrocytes. A low number of PAC1R-immunopositive astrocytes were detectable in the hippocampal area until 3 days after ischemia. PAC1R-positive astrocytes were widely distributed in the hippocampus between day 7 and day 14 after ischemia, and they were converging around the damaged CA1 pyramidal cell layer by day 28. These results suggest that PAC1R might be expressed in the middle to late stage of reactive astrocytes and PACAP plays an important role in the reactive astrocytes after brain injury.