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Objective: Traumatic brain injury (TBI) is one of the most common preventable causes of mortality and morbidity. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophysiological mechanisms underlying neuronal loss after TBI. Mildronate is demonstrated to be beneficial in various experimental models of ischemic diseases via anti-inflammatory, antioxidant, and neuroprotective mechanisms. This study aimed to investigate possible antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of mildronate in a rat model of TBI.Methods: A total of 46 male rats were divided into three groups of control, saline-treated TBI, and mildronate-treated TBI. Both TBI groups were subjected to closed-head contusive weight-drop injuries followed by treatment with saline or mildronate (100 mg/kg) administered intraperitoneally. The forebrain was removed 24 h after trauma induction, the activities of myeloperoxidase (MPO) and caspase-3, levels of superoxide dismutase (SOD), luminol- and lucigenin-enhanced chemiluminescence were measured, and histomorphological evaluation of cerebral tissues was performed.Results: Increased MPO and caspase-3 activities in the vehicle-treated TBI group (p < 0.001) were suppressed in the mildronate-treated TBI group (p < 0.001). Similarly, increase in luminol and lucigenin levels (p < 0.001 and p < 0.01, respectively) in the vehicle-treated TBI group were decreased in the mildronate-treated TBI group (p < 0.001). Concomitantly, in the vehicle-treated TBI group, TBI-induced decrease in SOD activity (p < 0.01) was reversed with mildronate treatment (p < 0.05). On histopathological examination, TBI-induced damage in the cerebral cortex was lesser in the mildronate-treated TBI group than that in other groups.Conclusion: This study revealed for the first time that mildronate, exhibits neuroprotective effects against TBI because of its anti-inflammatory, antiapoptotic, and antioxidant activities. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress following traumatic brain injury (TBI) leads to further deterioration of brain damage. Mildronate, known for its vasodilator and anticonvulsant effects, has been shown to be useful in a variety of experimental models and ischemic diseases. In this study, it was aimed to investigate possible antioxidant and neuroprotective effects of mildronate in a rat TBI model. Methods: Under ketamine anesthesia, TBI (n=20) was induced by dropping a metal weight (300 g) from a height of 70 cm on the skull of male Wistar albino rats. Half of the rats was treated intraperitoneally with vehicle, while the other half was treated with mildronate (100 mg/kg) immediately after TBI. Control group (n=8) was not exposed to any trauma. Twenty-four hours after TBI, transcardial paraformaldehyde perfusion was performed and brain injury was graded histopathologically following hematoxylin-eosin staining. Activities of myeloperoxidase (MPO) -marker of neutrophil infiltration-, apoptosis-marker caspase-3, antioxidant superoxide dismutase (SOD) and catalase (CAT), and levels of luminol- and lucigenin-enhanced chemiluminescence (CL) were measured in brain tissues. The data were evaluated by one-way ANOVA. Results: In the mildronate-treated group, the damage in the cerebral cortex that has occurred due to TBI was lighter compared to that of the vehicle-treated TBI group. Antioxidant SOD activity, which was found to be decreased in the brain tissues of the vehicle-treated TBI group (p<0.01), was increased in the group that has received mildronate treatment (p<0.05). Higher levels of CL, increased MPO and caspase-3 activities (p<0.01- 0.001) in the vehicle-treated TBI group were found to be suppressed in the mildronate-treated group (p<0.05-0.001). Conclusion: Suppression of oxidative damage and apoptosis in brain tissues of rats in mildronate-treated TBI group, and alleviation of brain damage by stimulating antioxidant systems suggest that mildronate should be further evaluated for its possible therapeutic effect in traumatic brain injury. [ABSTRACT FROM AUTHOR]