Ischemic stroke (IS) constitutes focal brain tissue hypoxia and hypoperfusion secondary to cerebral vessel occlusion, resulting in neuronal injury. This study aimed to investigate the expression pattern and mechanism of LARP7 in IS progression, and to explore whether upregulation of LARP7 attenuates neuronal injury by regulating endothelial cell autophagy. Focal cerebral ischemia was established via the middle cerebral artery occlusion (MCAO) model. Neurological function was assessed using the modified Garcia and Zea Longa scales, and infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining. LARP7 overexpression was achieved in rats and brain microvascular endothelial cells (BMECs) via lentiviral transduction. LARP7 and autophagy-related protein levels were measured by qRT-PCR and Western blotting. Neuronal morphology was evaluated using hematoxylin–eosin (HE) and Nissl staining. Autophagic activity was determined by CD31/LC3 immunofluorescence, LC3 detection, and monodansylcadaverine (MDC) staining. The autophagy inhibitor 3-methyladenine (3-MA) was administered both in vitro and in vivo. Inflammatory factors, apoptotic rate, and brain injury markers were subsequently detected. LARP7 expression was significantly decreased in MCAO rat brain tissue. LARP7 overexpression improved neurological scores, reduced neuronal damage, and diminished infarct volume and brain injury markers. In BMECs, LARP7 overexpression enhanced autophagic activity, as evidenced by increased LC3-II and decreased p62 levels. 3-MA treatment reversed the protective effects of LARP7 overexpression, elevating inflammatory cytokines, apoptotic rate, and infarct volume. LARP7 is downregulated following IS. LARP7 overexpression alleviates ischemic neuronal injury by promoting BMEC autophagy, whereas autophagy inhibition exacerbates brain damage. These findings highlight LARP7-mediated endothelial autophagy as a critical neuroprotective mechanism in IS, providing a potential therapeutic target for IS intervention.
Shao et al. (Tue,) studied this question.