ABSTRACT
Objective To study the effects of fluorocitrate (FC),astrocytic metabolic inhibitor,on early brain injury after subarachnoid hemorrhage (SAH)in rats so as to explore the mechanism of early brain injury mediated by astrocyte after SAH.Methods Thirty six SD male rats were randomly divided into sham group,SAH 3 d group and SAH 3 d+FC group,with 12 rats in each group.The model of SAH was established by an endovascular perforation technique. FC was injected into the lateral ventricle. Three days after SAH, the expressions of GFAP,Iba-1 and TNF-α were detected using immunohistochemistry in all rats.The expression and phosphorylation of NF-κB in the nucleus were detected by Western blot.The expressions of TNF-α,IL-1βand IL-6 were detected by ELISA.Cell apoptosis was detected by TUNEL.Results Neuronal swelling,nuclear anomalies, disorganization of micrangium,abnormality of endothelial cells appeared in SAH 3 d group,but not in sham group. The expressions of NSE,GFAP and Iba-1 were significantly increased in SAH 3 d group compared with those in sham group (all P＜0.05).The number of apoptotic cells was increased.The expression and phosphorylation of NF-κB were significantly increased.The expressions of TNF-α,IL-1β and IL-6 were significantly increased.However, neuronal injuries were alleviated by injecting FC.The expressions of NSE,GFAP and Iba-1 in SAH 3 d+FC group were inhibited.The number of apoptotic cells in SAH 3 d+FC group was decreased compared with that in SAH 3 d group.The expression and phosphorylation of NF-κB were decreased by FC.The expressions of TNF-α,IL-1β and IL-6 were significantly decreased by FC (P＜0.05).Conclusion Astrocytes may play an important role in early brain injury after SAH,underlying the mechanism that they released TNF-α,IL-1βand IL-6 and activate microglia by activating NF-κB signal.The inhibition of excess activation of astrocytes may plays a protective role in early brain injury after SAH.