The Study Of The Protective Effects Of Deferoxamine On Cognitive Dysfunction After Experimental Subarachnoid Hemorrhage In Rats

Objective: To establish subarachnoid hemorrhage(SAH) model and to investigate the effects and mechanisms of deferoxamine(DFO) on cognitive dysfunction after experimental subarachnoid hemorrhage.Methods: 64 adult male SD rats were randomly divided into four groups: Sham group, SAH group and SAH+Saline group and SAH+DFO group. All SAH rats were subjected to injection of 300 ?l fresh autologous arterial blood from the femoral artery into the prechiasmatic cistern within 20 sec. The rats in the sham group accepted the same operative procedures except injecting the blood. Rats in SAH+DFO group were subjected to intraperitoneal injection of DFO at a dosage of 30 mg/kg every 12 hours after SAH. The SAH+Saline group were subjected to intraperitoneal injection of equal volume of normal saline instead of DFO. Changes in body weights of rats in all groups were recorded. Cognitive and memory abilities were investigated by the Morris water maze at 48 hours after the induction of SAH. Brain tissues were obtained for Nissl staining and histological and biochemical tests. The hippocampus tissues were taken to analyze the iron levels, reactive oxygen species(ROS), malondialdehyde(MDA) contents, and superoxide dismutase(SOD) activities.Results: The rat mortality was 25.6 % in the SAH group and was 0 % in the sham group. There was no significant difference in mortality between the SAH+DFO group and the SAH+Saline group(P > 0.05). Body weights of SAH rats were significantly lower than that of the sham group at 1 and 2 days after SAH(P<0.05). In the Morris water maze test, the rat learning and memory abilities in the SAH group were significantly declined comparedwith the sham-operated rats(P<0.05). Compared with the placebo group, the learning and memory abilities of rats in the SAH+DFO group were significantly improved(P<0.05). Nissl staining showed a large number of neuronal loss in the hippocampus of SAH rats, which was obviously relieved by DFO. The levels of iron, ROS contents were significantly increased after SAH(P<0.05), and were obviously decreased after DFO treatment(P<0.05). The SOD activity was obviously decreased after SAH(P<0.05) and significantly elevated after treatment of DFO(P<0.05).Conclusion: 1, cognitive dysfunction can be found after SAH; 2, the iron overload after SAH, which aggravates the oxidative brain injury, may be one of the mechanisms of cognitive dysfunction. 3, deferoxamine improve the cognitive dysfunction after SAH probably via chelating iron overload and diminishing oxidative injury.