Knockdown of fatty acid binding protein 3 attenuates cerebral Ischemia-reperfusion injury via inhibiting neuronal apoptosis in mice

Background: Stroke remains a leading cause of death and disability worldwide, with ischemic stroke accounting for approximately 87% of cases. Although timely reperfusion is crucial for salvaging the ischemic penumbra, it can paradoxically exacerbate tissue damage through ischemia-reperfusion (I/R) injury. Recent studies have demonstrated that I/R significantly upregulates fatty acid binding protein 3(FABP3) expression, which has been shown to play a crucial role in mitochondrial dysfunction and neuronal apoptosis. However, the role of FABP3 in cerebral I/R injury remains poorly understood. Methods: Adult male C57BL/6 mice underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by 24 h of reperfusion. Mice were randomly assigned to four groups (n = 5 per group): control (sham), model (I/R), negative control (sh-NC I/R), and experimental group (sh-FABP3 I/R). FABP3-specific shRNA lentivirus was administered via intracerebroventricular injection. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological function by behavioral scoring, and neuronal damage by hematoxylin-eosin (H&E) staining. Western blot analysis was performed to evaluate the expression of apoptosis-related proteins. Results: FABP3 expression was significantly upregulated following cerebral I/R injury. FABP3 knockdown markedly reduced infarct volume (20 ± 3.16% vs. 35 ± 2.43% in I/R group, p FABP3 knockdown reduces infarct volume and neurological deficits after cerebral ischemia‑reperfusion injury by suppressing neuronal apoptosis, suggesting FABP3 is a potential therapeutic target. FABP3 is significantly up-regulated in mouse brain after transient cerebral I/R injury.Intracerebroventricular FABP3-shRNA lentivirus was used to down-regulate FABP3 expression in tMCAO mice.FABP3 inhibition reduces infarct volume and improves neurological scores. FABP3 knockdown suppressing neuronal apoptosis.FABP3 is a potential therapeutic target for ischemic stroke. FABP3 is significantly up-regulated in mouse brain after transient cerebral I/R injury. Intracerebroventricular FABP3-shRNA lentivirus was used to down-regulate FABP3 expression in tMCAO mice. FABP3 inhibition reduces infarct volume and improves neurological scores. FABP3 knockdown suppressing neuronal apoptosis. FABP3 is a potential therapeutic target for ischemic stroke.