Neuroprotective Mechanisms Of Deferoxamine Attenuates Early Brain Injury Following Subarachnoid Hemorrhage In Rats

Objectives:Early brain injury（EBI）is the important cause of subarachnoid hemorrhage（SAH）to severely damage the prognosis of patients.Deferoxamine（DFX）is an iron chelator that has been shown to have beneficial effects in neurological disorders in recent years,but its mechanism for EBI after SAH remains unclear.This study investigates the effect of DFX therapy on EBI and its mechanism.Methods:Seventy-two healthy adult male Sprague-Dawley rats were randomly divided into Sham group,SAH group and DFX group,each group consisted of 24 animals.The SAH model was constructed by performing endovascular perforation on rats.100 mg/kg of DFX was injected into the DFX group at the 2nd and 6th hours after SAH,and then every 12 hours for 3 days.The remaining two groups were injected with equal amounts of saline at the same time.Assessment of neurological function in rats using a modified Garcia test and balance beam test.Brain edema,blood-brain barrier（BBB）integrity,and apoptosis rate were detected using the dry weight method,Evan’s blue staining,and TUNEL staining,respectively.The expression level of AQP4 mRNA was measured by conducting quantitative real-time PCR,the expression of AQP4 and GFAP proteins was detected by immunofluorescence staining,and the expression levels of related proteins was measured by western blot.Results:Compared with the Sham group,DFX therapy significantly improved neurological function,reduced cerebral edema,the extent of cortical apoptosis,and BBB damage within 72 h.The levels of AQP4 and apoptosis-related protein Bax/cleaved caspase-3 were significantly lower than those in the SAH group.In contrast,the levels of anti-apoptotic protein Bcl-2 and tight junction protein ZO-1/Claudin-5 were higher than those in the SAH group.Meanwhile,our study found that treatment with DFX resulted in activation of the classical PI3K/Akt signaling pathway.Conclusions:Our findings substantiate the potency of DFX therapy in assuaging EBI following SAH via activating the PI3K/Akt signaling pathway to attenuate brain edema and neuronal apoptosis.