Neuroprotective Mechanism Of FGF-2 On Autophagy Regulation In Early Brain Injury Following Subarachnoid Hemorrhage

Objective: The degree of early brain injury(EBI)is a significant factor affecting the prognosis of subarachnoid hemorrhage(SAH).Relevant studies showed that fibroblast growth factor-2(FGF-2)may reduce the serious consequences of EBI after SAH.However,the mechanism has not been verified.Therefore,we explored the potential mechanism of neuroprotective effects of FGF-2 by performing SAH model on SpragueDawley(SD)rats.Materials and Methods: FGF-2 was administered intranasally to rats in treatment group within 30 min after modeling.Rapamycin or LY294002 was administered within half an hour before modeling.Further research was carried out by the following methods: neurological scale,brain water content,TUNEL staining,Western blot,and immunofluorescence staining,etc.Results: The results revealed that FGF-2 reduced the number of TUNEL positive cells,decreased brain water content,and improved the neurological function of rats after SAH.Additionally,the expression of autophagy-related proteins(LC3 and Beclin-1)was obviously decreased in FGF-2 treatment group compared with SAH+vehicle group.The therapeutic effect of FGF-2 in SAH+FGF-2+rapamycin group was weaker than that in SAH+FGF-2 group.After inhibiting PI3K/Akt pathway,the expression of LC3 and Beclin-1 was increased and the therapeutic effect of FGF-2 was weaker than FGF-2 treatment group.Conclusion: These results inferred that FGF-2 may suppress autophagy to play a neuroprotective role.The underlying mechanism may,at least partially,involve the PI3K/Akt pathway.These evidence supports the possibility of FGF-2 as a new solution of treatment for SAH.