Lysophosphatidic Acid Receptor 5 Plays a Pathogenic Role in Brain Damage after Focal Cerebral Ischemia by Modulating Neuroinflammatory Responses.

Cells
Arjun SapkotaJi Woong Choi

Abstract

Receptor-mediated lysophosphatidic acid (LPA) signaling has come to be considered an important event for various diseases. In cerebral ischemia, LPA1 has recently been identified as a receptor subtype that mediates brain injury, but the roles of other LPA receptor subtypes remain unknown. Here, we investigated the potential role of LPA5 as a novel pathogenic factor for cerebral ischemia using a mouse model of transient middle cerebral artery occlusion (tMCAO). LPA5 was upregulated in the ischemic core region after tMCAO challenge, particularly in activated microglia. When TCLPA5, a selective LPA5 antagonist, was given to tMCAO-challenged mice immediately after reperfusion, brain damage, including brain infarction, functional neurological deficit, and neuronal and non-neuronal apoptosis, was reduced in mice. Similarly, delayed TCLPA5 administration (at three hours after reperfusion) reduced brain infarction and neurological deficit. The histological results demonstrated that TCLPA5 administration attenuated microglial activation, as evidenced by the decreased Iba1 immunoreactivities, the number of amoeboid cells, and proliferation in an injured brain. TCLPA5 administration also attenuated the upregulation of the expression of pr...Continue Reading

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Citations

Oct 8, 2020·Biomolecules & Therapeutics·Arjun SapkotaJi Woong Choi
Nov 6, 2020·Neuromolecular Medicine·Eric Birgbauer
Nov 19, 2020·International Journal of Molecular Sciences·Chi-Ho LeeJi Woong Choi
Aug 1, 2021·BMC Medical Informatics and Decision Making·Yue LiuBenzheng Wei
Aug 8, 2021·International Journal of Molecular Sciences·Bhakta Prasad Gaire, Ji-Woong Choi

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Methods Mentioned

BETA
PCR

Clinical Trials Mentioned

NCT01766817
NCT02763969
NCT01651143

Software Mentioned

ImageJ
GraphPad
GraphPAD Prism
Adobe Photoshop Elements

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