Traumatic brain injury (TBI) is a primary public health concern that has caused millions of deaths and disabilities around the world. Numerous medications are available to relieve TBI-associated complications. However, these medications do not prevent further harm from occurring. Therefore, the unmet need is the development of novel therapeutic medicines that protect against neuronal damage as a result of trauma and its repercussions, especially from secondary injury. We present a study using

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... iss albino mice (25-30 g) of either sex to address the therapeutic issues concerning TBI. In our study, TBI was induced by the weight-drop method. Oxidative stress parameters were observed following the administration of zonisamide (100 mg/kg) and Nigella sativa (NS) (300 mg/kg) per se and in combination. The levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were observed to be significantly enhanced, but the levels of malondialdehyde (MDA) and nitric oxide (NO) were significantly reduced by treatment with the mentioned dugs. Our findings affirmed the potential function of both drugs in preventing TBI-induced oxidative damage.