BMS-986020, a Specific LPA(1) Antagonist, Provides Neuroprotection against Ischemic Stroke in Mice
- Authors
- Gaire, B.P.; Sapkota, A.; Choi, J.W.
- Issue Date
- Nov-2020
- Publisher
- MDPI AG
- Keywords
- Angiogenesis; BMS-986020; Long-term neuroprotection; Neurogenesis; Neuroprotective effects; Transient middle cerebral artery occlusion (tMCAO)
- Citation
- Antioxidants, v.9, no.11, pp.1 - 14
- Journal Title
- Antioxidants
- Volume
- 9
- Number
- 11
- Start Page
- 1
- End Page
- 14
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79120
- DOI
- 10.3390/antiox9111097
- ISSN
- 2076-3921
- Abstract
- Stroke is a leading cause of death. Stroke survivors often suffer from long-term functional disability. This study demonstrated neuroprotective effects of BMS-986020 (BMS), a selective lysophosphatidic acid receptor 1 (LPA1) antagonist under clinical trials for lung fibrosis and psoriasis, against both acute and sub-acute injuries after ischemic stroke by employing a mouse model with transient middle cerebral artery occlusion (tMCAO). BMS administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, neurological deficits, and cell apoptosis at day 1 after tMCAO. Neuroprotective effects of BMS were preserved even when administered at 3 h after reperfusion. Neuroprotection by BMS against acute injuries was associated with attenuation of microglial activation and lipid peroxidation in post-ischemic brains. Notably, repeated BMS administration daily for 14 days after tMCAO exerted long-term neuroprotection in tMCAO-challenged mice, as evidenced by significantly attenuated neurological deficits and improved survival rate. It also attenuated brain tissue loss and cell apoptosis in post-ischemic brains. Mechanistically, it significantly enhanced neurogenesis and angiogenesis in injured brains. A single administration of BMS provided similar long-term neuroprotection except survival rate. Collectively, BMS provided neuroprotection against both acute and sub-acute injuries of ischemic stroke, indicating that BMS might be an appealing therapeutic agent to treat ischemic stroke. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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