The preventive effect of the mexiletine on cerebral ischemic injury following experimental middle cerebral artery occlusion

Occurence of free radicals, intracellular sodium and calcium accumulation, and lipid peroxidation has crucial role in developing brain ischemic injury. In our study we investigated the effects of the mexiletine on brain ischemic injury. Mexiletine has some important features in the prevention of ischemic brain injury such as, sodium and calcium canal blockage and prevention of the free radical occurence. Previous studies demonstrated that mexiletine has beneficial effect on spinal cord injury and cerebral vasospasm following subarachnoid hemorrhage. In this study, thirty adult-male Spraque-Dawley rats weighting between 285 and 425 grams were used. Left middle cerebral artery occlusion were performed following microcraniectomy and simultaneous bilateral carotid artery occlusion were performed. One hour later carotid clips were removed. Animals were separated into three different groups. There were ten rats in each group. All rats in three groups insulted with ischemia. There were no drug application to the rats in control group, saline were applied to the rats in sham group, mexiletine were applied to the rats in treatment group. After twenty four hours from ischemic insult, all rats were decapitated following sacrification using high dose anesthetic agent. Following whole brain extraction from the cranium, brains were kept in the 10 % formaldehit solution for one or two days. Brains were rostrocaudally embedded in paraffin blocks following standard tissue treatment to the brains. Paraffin blocks were treated according to our procedure. After this procedure, paraffin blocks were cut with microtome which was arranged for cutting into paraffin blocks to the thickness 20μm of slices. All slices were dyed with hemotoxilen-eosine (H&E). After the dying of the slices, cerebral infarct volumes were calculated using computer and appropriate software programs. Cerebral infarct volumes were compared using ANOVA (Analysis of variance) and Post- Hoc Bonferroni test. The results showed statistically significant (p<0,0001) differences between treatment group (81,98 ± 12,58mm³) and control (121,57 ± 11,41mm³) and sham (116,08 ± 12,36mm³) groups. Mexiletine should be considered as an alternative medication for prevention and treatment of the ischemic brain injury due to its multipotent effects and further experimental studies are needed.