Role of the PGE₂ receptor subtypes EP1, EP2, and EP3 in repetitive traumatic brain injury

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.

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

“…These observations are inconsistent with the ndings where alleviation in expression of NLRP3/NFkB reduced microglial activation and proin ammatory cytokines [84,85]. Both ValS an SC19220 rescued microglial and astrocyte activation as their (COX-1/EP1) predominance in those cells thus ameliorated neurogenic niches perturbations.…”

The utilization of small non‐mammals in traumatic brain injury research: A systematic review

“…On the other hand, the mammalian TBI model is more advanced in its robust research background focusing on the mechanism and important biomarkers. 117,[163][164][165][166][167][168] In addition to that, non-mammalian research has not conducted any research on inducing stem cell for brain injury as been conducted previously in this study with mammalian model. 169,170 Indeed, one of the study showed successful xenotransplantation of human iPSC-derived NSCs and isogenic neural cell progenies in a mouse model.…”

Traumatic brain injury

“…The research group of Ibarra reveals that immunization with neural derived peptides possesses neurogenic and regenerative properties which render motor and sensitive recovery in the chronic stage of SCI 10 . Such combined targeting of neurogenesis and regeneration may be similarly applied to TBI, since the pathology of TBI manifests with impaired stem cell potencies, as recognized in the cell therapy campaign noted in the other papers described here 5‐7 …”

“…Recognizing that cell therapy may not be a magic bullet, Willing and co‐workers 7 offer a combination therapy. Here, they show the potential of combining cell therapy with drugs that target signaling pathways of the neuro‐immune‐inflammatory axis.…”

“…The articles in this special issue probe the pathology of CNS trauma, including TBI and SIC, and begin to understand potential therapeutic modalities. Along this line, the proposed cell therapy 5‐7 and drug and immunization treatments 8‐10 offer new directions in the management of TBI. These promising therapies warrant serious consideration as we translate them into clinical applications.…”