Role of the PGE2 receptor subtypes EP1, EP2, and EP3 in repetitive traumatic brain injury. (16th October 2019)

• Record Type: Journal Article
• Authors: Catlin, James; Leclerc, Jenna L.; Shukla, Krunal; Marini, Sarah M.; Doré, Sylvain
• Other Names: Bailes Julian E. guestEditor.; Borlongan Cesar V. guestEditor.
• Is Part Of: CNS neuroscience & therapeutics. Volume 26:Number 6(2020)
• Page Start: 628
• Page End: 635
• Publication Date: 2019-10-16
• Subjects: concussion -- eicosanoids -- EP receptors -- prostanoids -- repetitive head injury; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.13228
• Languages: English
• ISSNs: 1755-5930

Abstract

Abstract: Aims: The goal was to explore the signaling pathways of PGE2 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 PGE2 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 PGE2 EP receptors may be potential therapeutic targets to treat repetitive concussions and other acute brain injuries.