Effects of Withania Somnifera on Stress Response, Neuroinflammation, and Brain Histopathology in a Mouse Model of Traumatic Brain Injury

Traumatic Brain Injury (TBI) is a debilitating neurological condition resulting from external mechanical forces, often leading to cognitive impairment, neuroinflammation, and oxidative stress. Current therapeutic strategies offer limited efficacy in reversing TBI-induced neuronal damage. Ashwagandha (Withania somnifera), a traditional Ayurvedic herb, is known for its neuroprotective and anti-inflammatory properties. This study aimed to evaluate the therapeutic potential of Ashwagandha in a controlled cortical impact (CCI)-induced TBI model in adult male C57BL/6 mice. Animals were divided into four groups: Sham Control, TBI Control, TBI + Vehicle, and TBI + Ashwagandha (500 mg/kg body weight for 14 days post-injury). Behavioral assessments (Y-maze and Morris water maze) revealed that Ashwagandha significantly alleviated TBI-induced hyperactivity, though memory deficits persisted. Biochemical analyses showed a marked reduction in oxidative stress markers (Catalase, CAT, Superoxide dismutase SOD) and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) in the Ashwagandha-treated group. Histopathological and immunohistochemical evaluations demonstrated preserved neuronal architecture and decreased astrocytic (GFAP) and microglial (Iba-1) activation. These findings indicate that Ashwagandha effectively mitigates neuroinflammation, reduces oxidative damage, and improves histological outcomes in TBI mice. In conclusion, Ashwagandha exhibits significant neuroprotective effects and may serve as a promising adjunct therapy for managing TBI-induced neuropathology.