bFGF Knockdown Inhibits mTOR Signaling by Suppressing Caveolin-1 and Aggravates Cognitive Damage After Arterial Ischemic Brain Injury in Juvenile Rats.

Abstract

Pediatric arterial ischemic stroke (AIS) is the leading cause of stroke in children and approximately two-thirds of affected patients experience permanent neurological sequelae. Although basic fibroblast growth factor (bFGF) has positive effects on neural development, axon regeneration, and synaptic reconstruction, its effects in AIS remain unclear. Here, we examined the role of bFGF in post-ischemic cognitive function in juvenile rats. Behavioral assessments using the Morris water maze and the three-chamber test revealed that bFGF knockdown impairs spatial learning, memory, and social interactions. Golgi staining and electron microscopy demonstrated that bFGF knockdown disrupts neuronal axon morphology and synaptic ultrastructure. In the hippocampus of AIS rats, bFGF deficiency significantly reduced PSD95 and synapsin I protein levels. Moreover, bFGF knockdown decreased autophagy and apoptosis markers while increasing necrosis indicators. Mechanistically, loss of bFGF inhibited phosphorylation of mammalian target of rapamycin (mTOR), a process regulated by fibroblast growth factor receptor 1 (FGFR1). We further show that bFGF interacts with FGFR1 and caveolin-1 (Cav1), a membrane scaffold protein; knockdown of Cav1 in the hippocampus similarly attenuated mTOR signaling. Collectively, our results suggest that bFGF deficiency suppresses Cav1, thereby inhibiting mTOR signaling and exacerbating cognitive deficits after AIS in juvenile rats. These findings provide insight into the molecular mechanisms underlying pediatric AIS.