Role of the PGE(2) receptor subtypes EP1, EP2, and EP3 in repetitive traumatic brain injury

AIMS: The goal was to explore the signaling pathways of PGE(2) to investigate therapeutic effects against secondary injuries following TBI. METHODS: Young (4.9 ± 1.0 months) and aged (20.4 ± 1.4 months) male wild type (WT) C57BL/6 and PGE(2) EP1, 2, and 3 receptor knockout mice were selected to either receive sham or repetitive concussive head injury. Immunohistochemistry protocols with Iba1 and GFAP were performed to evaluate microgliosis and astrogliosis in the hippocampus, two critical components of neuroinflammation. Passive avoidance test measured memory function associated with the hippocampus. RESULTS: No differences in hippocampal microgliosis were found when aged EP2(−/−) and EP3(−/−) mice were compared with aged WT mice. However, the aged EP1(−/−) mice had 69.2 ± 7.5% less hippocampal microgliosis in the contralateral hemisphere compared with WT aged mice. Compared with aged EP2(−/−) and EP3(−/−), EP1(−/−) aged mice had 78.9 ± 5.1% and 74.7 ± 6.2% less hippocampal microgliosis in the contralateral hemisphere. Within the EP1(−/−) mice, aged mice had 90.7 ± 2.7% and 81.1 ± 5.6% less hippocampal microgliosis compared with EP1(−/−) young mice in the contralateral and ipsilateral hemispheres, respectively. No differences were noted in all groups for astrogliosis. There was a significant difference in latency time within EP1(−/−), EP2(−/−), and EP3(−/−) on day 1 and day 2 in aged and young mice. CONCLUSION: These findings demonstrate that the PGE(2) EP receptors may be potential therapeutic targets to treat repetitive concussions and other acute brain injuries.