SRSF3 Alleviates Ischemic Cerebral Infarction Damage by Activating the PI3K/AKT Pathway

Abstract

Background: Ischemic cerebral infarction is one of cerebrovascular diseases with high incidence, disability rate, and mortality globally, and neuronal cell apoptosis is a crucial cause of brain injury during cerebral infarction. Methods: A middle cerebral artery occlusion (MCAO) model was built in Sprague-Dawley rats to simulate ischemic cerebral infarction. An in vitro model of ischemic cerebral infarction was constructed in BV2 cells with the treatment of oxygen-glucose deprivation (OGD). The role and mechanism of serine/arginine-rich splicing factor 3 (SRSF3) in ischemic cerebral infarction were investigated both in animal and cell models. Results: The expression of SRSF3 was downregulated in MCAO-treated rats. Overexpression of SRSF3 reduced the neurological scores, brain water content, and infarct volume in MCAO-induced rats. Increased apoptosis in neurons accompanied with the abnormal expressions of apoptosis-related proteins in MCAO-induced rats were revised with the upregulation of SRSF3. Also, a diminished cell viability and elevated apoptosis rate were indicated in OGD-induced BV2 cells, which were reversed with the overexpression of SRSF3. Besides, OGD induced an enhancement in the relative protein expression of programmed cell death protein 4 (PDCD4) and a reduction in the relative expression of p-PI3K/PI3K and p-AKT/AKT, which were inverted with the upregulation of SRSF3 in BV2 cells. Overexpression of PDCD4 abolished the role of SRSF3 in cell viability, apoptosis rate, and the level of the PI3K/AKT pathway in OGD-induced BV2 cells. Conclusion: SRSF3 improved ischemic cerebral infarction via PDCD4 in vivo and in vitro, which was closely associated with the PI3K/AKT signaling pathway.