DOI: 10.6084/m9.figshare.29899433
title: Knockdown of fatty acid binding protein 3 attenuates cerebral Ischemia-reperfusion injury <i>via</i> inhibiting neuronal apoptosis in mice

description: 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 (<i>n</i> = 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 <i>via</i> 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% <i>vs</i>. 35 ± 2.43% in I/R group, <i>p</i> &lt; 0.001) and improved neurological scores. Histological analysis revealed that FABP3 inhibition significantly attenuated neuronal damage in the penumbra cortex and hippocampal Cornu Ammonis area 1(CA1) region. Moreover, FABP3 knockdown decreased the expression of pro-apoptotic proteins (Bax, cleaved-caspase-3) while increasing anti-apoptotic Bcl-2 levels. Conclusions: This study demonstrates for the first time that FABP3 knockdown confers neuroprotection against cerebral I/R injury by suppressing neuronal apoptosis. These findings suggest that FABP3 is a promising therapeutic target for ischemic stroke treatment. 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.