Experimental Research On Early Brain Injury Protection Of Intranasal Administration Of Granulocyte Colony Stimulating Factor Following Subarachnoid Hemorrhage

Objective: To explore whether intranasal administration of recombinant human granulocyte colony stimulating factor(rhGCSF) can relieve early brain injury following experimental subarachnoid hemorrhage(SAH).Methods:1. Rat SAH model was induced by double injection of autologous blood into the cisterna magna. 48 rats were randomizedly assigned into normal group, SAH group, intranasal administration of normal saline(NS) group (SAH+ NS group) and intranasal administration of rhGCSF group(SAH+rhGCSF group).2. Regional cerebral blood flow (rCBF) of cerebral cortex was observed using a Laser Doppler Flowmeter(LDF)probe. Neurological function assessment was inducted by movement and sensibility at 24 hours after secondary cisternal injection in rats. The diameter, perimeter and cross-sectional area of basilar artery(BA) lumen were measured to evaluate the degree of cerebral vasospasm.Coronal sections were made to observe the neuropathology of the cortex and the CA1 region of the hippocampus. Brain water content was surveyed by dry/wet weight.The expression of AQP4 in brain tissue was detected by immunohistochemistry .Superoxide dismutase (SOD) activity and content of malondialkhyde (MDA) in the brain tissue homogenate were detected by chemical method.Results:1.The rCBF decreased immediately after secondary injection, the rCBF in SAH+rhGCSF group rised quicked as compared with that in SAH group and SAH+ NS group.2.Neurological function assessment was 18 scores in normal group,and the scores were significantly lowered in SAH group and SAH+NS group, rhGCSF treatment was obviously improved.3.Compared with normal group, the number of neuron cells in cortex and hippocampal CA1 region were significantly reduced, the structural arrangement was disordered and morphology was abnormal in SAH group and SAH + NS group, rhGCSF treatment could relieve this injury.4.Compared with normal group, the diameter, perimeter and cross-sectional area of BA were significantly decreased, endothelial cell swelled,inflammatory cell infiltrated,rhGCSF can partially attenuate this injury. 5.Compared with normal group, SOD activity was significantly decreased and the content of MDA was significantly increased at 24 hours after SAH induction. There is no statistically significant difference between SAH group and SAH+NS group(P>0.05). The content of MDA was decreased (P < 0.05)and SOD activity was increased ( P < 0.01) in SAH+rhGCSF group compared with SAH group and SAH+NS group.6.Compared with normal group, brain water content significantly increased after SAH induction. Intranasal administration of rhGCSF can attenuate global brain edema.7.Compared with normal group, the AQP4 was significantly up-regulated in SAH group and SAH+NS group, and was marked in the basal cerebral cortex,the expression was down-regulated in SAH+rhGCSF group(P<0.01),but still to remain higher compared with normal group(P<0.01).Conclusion: Intranasal administration of rhGCSF can relieve early brain injury after SAH in rats, including ameliorating cortical rCBF, relieving oxygenic free radicals and brain edema, partially attenuating cerebral vasospasm.