BACKGROUND: The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model. METHODS: One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis. RESULTS: The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05). CONCLUSIONS: This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.
BACKGROUND: The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model. METHODS: One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis. RESULTS: The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05). CONCLUSIONS: This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.
Authors: Mutsumi Fujii; Junhao Yan; William B Rolland; Yoshiteru Soejima; Basak Caner; John H Zhang Journal: Transl Stroke Res Date: 2013-08 Impact factor: 6.829