Neuroprotective effects of edaravone on early brain injury in rats after subarachnoid hemorrhage.
- Author:
Yang GAO
1
;
Xin-sheng DING
;
Shu XU
;
Wei WANG
;
Qi-long ZUO
;
Feng KUAI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antipyrine; analogs & derivatives; therapeutic use; Blotting, Western; Brain Injuries; drug therapy; etiology; Immunohistochemistry; Male; Malondialdehyde; metabolism; Neuroprotective Agents; therapeutic use; Random Allocation; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; physiopathology; Superoxide Dismutase; metabolism
- From: Chinese Medical Journal 2009;122(16):1935-1940
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDThe 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.
METHODSOne 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.
RESULTSThe 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).
CONCLUSIONSThis 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.
