Search

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Apigenin is a plant flavone proven with biological properties such as anti-inflammatory, antioxidant, and antimicrobial effects. This study, it was aimed to examine the possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of the mild traumatic brain injury (TBI) model. Wistar albino male rats were randomly assigned to groups: control (n = 9), TBI (n = 9), TBI + vehicle (n = 8), and TBI + apigenin (20 and 40 mg/kg, immediately after trauma; n = 6 and n = 7). TBI was performed by dropping a 300 g weight from a height of 1 m onto the skull under anesthesia. Neurological examination and tail suspension tests were applied before and 24 h after trauma, as well as Y-maze and object recognition tests, after that rats were decapitated. In brain tissue, luminol- and lucigenin-enhanced chemiluminescence levels and cytokine ELISA levels were measured. Histological damage was scored. Data were analyzed with one-way ANOVA. After TBI, luminol (p <.001) and lucigenin (p <.001) levels increased, and luminol and lucigenin levels decreased with apigenin treatments (p <.01–.001). The tail suspension test score increased with trauma (p <.01). According to the pre-traumatic values, the number of entrances to the arms (p <.01) in the Y-maze decreased after trauma (p <.01). In the object recognition test, discrimination (p <.05) and recognition indexes (p <.05) decreased with trauma. There was no significant difference among trauma apigenin groups in behavioral tests. Interleukin (IL)-10 levels, one of the anti-inflammatory cytokines, decreased with trauma (p <.05), and increased with 20 and 40 mg apigenin treatment (p <.001 and p <.01, respectively). The histological damage score in the cortex was decreased in the apigenin 20 mg treatment group significantly (p <.05), but the decrease observed in the apigenin 40 mg group was not significant. The results of this study revealed that apigenin 20 and 40 mg treatment may have neuroprotective effects in mild TBI via decreasing the level of luminol and lucigenin and increasing the IL-10 levels. Additionally, apigenin 20 mg treatment ameliorated the trauma-induced cortical tissue damage. [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]