Lysophosphatidic acid receptor 1 contributes to brain injury of mice challenged by permanent middle cerebral artery occlusion
Lysophosphatidic acid receptor 1 (LPA1) plays a critical role in brain injury following transient brain ischemic stroke. However, its role in brain injury following permanent brain ischemic stroke remains unknown. Here, we investigated whether LPA1 would contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO), and a selective LPA1 antagonist (AM152) was used as a pharmacological tool. When AM152 was given to pMCAO-challenged mice one hour after occlusion, the pMCAO-induced brain damage, such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption, was significantly attenuated. Through histological analyses, it was demonstrated that AM152 administration attenuated microglial activation and their proliferation in injured brain after pMCAO challenge. AM152 administration also decreased the expression levels of pro-inflammatory cytokines but increased those of anti-inflammatory cytokines. As underlying effector pathways, NF-kB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in the LPA1-dependent pathogenesis. Collectively, this study demonstrates that LPA1 can contribute to brain injury by permanent ischemic stroke, along with its relevant pathogenic events in the injured brain. This work was supported by grants (NRF-2021R1A2C1005520, NRF-2020M3A9E4104384, and NRF- 2020R1A6A1A03043708).
2024 Spring Convention