Targeting Inflammation in Traumatic Brain Injury and Neuroprotection Throgh Phytoconstituent Intervention

Abstract

Background: TBI is defined as impact, penetration, and fast movement of the brain within the skull which is responsible for the neurological dysfunction of the brain. Primary brain injury refers to damage caused by immediate physical impact. The secondary injury frequently progresses into severe damage that lasts from hours to years. In the TBI, MPO is found in infiltrated neutrophils which is responsible for the neuroinflammation in the brain. Trigonelline hydrochloride, a plant alkaloid shown neuroprotective effects instroke by reducing the myeloperoxidase level. So, it might improve the condition of trauma patients. The main aim of the present study is to investigate the effect of trigonelline against weight drop-induced TBI in Rats. Experimental Design: In this study, Wistar Rats were assigned into six groups. Normal control, traumatic brain injury (Disease Controlled Group), Three treatment groups i.e., (TBI + TG (25 mg/kg), TBI + TG (50 mg/kg), TBI + TG (100 mg/kg) and one standard group TBI + Standard (TBI + 4-ABAH, 100 mg/kg). Six animals were taken in each group. The dose was given through the i.p route. Trigonelline was daily administered for three days before the TBI exposure, with the last injection made 1 hour pre-injury. The vehicle will be administered in the control group. Trauma was induced in rats by Marmarou’s weight drop method. Finally, after one day of the brain injury, behavioural parameters like actophotometer, rotarod, beam walk, rearing test and Y-maze were performed and then rats were sacrificed and their brains were isolated for estimation of Biochemical parameters like myeloperoxidase level estimation, level of LPO, nitrite level, reduced glutathione, catalase, SOD, TNF-α as well as histopathological studies. Result: This study found that the effect of trigonelline hydrochloride is promising as a neuroprotective therapeutically in TBI. Trigonelline hydrochloride helps the improvement of locomotor and motor coordination deficiency in the treatment group compared to the disease control group. A low dose of trigonelline hydrochloride (25mg/kg) does not show any significant improvement in behavioural parameters, biochemical estimation as well as histopathology studies. Medium dose (50 mg/kg) and High dose (100 mg/kg) were able to show a significant improvement compared to the disease control group. Trigonelline significantly improved neuroprotection against myeloperoxidase estimation, lipid peroxidation, nitric oxide, reduced glutathione, catalase as well as TNF-α. The histopathology shows a decrease in vasogenic edema and lesions in the TG-treated group in contrast to the disease-manifested group. Conclusion: Our results found that trigonelline hydrochloride, through its inhibition of MPO level, demonstrates effectiveness in attenuating the behavioural, biochemical, and histopathological repercussions of brain injury so it is a promising therapeutic agent for the treatment and management of TBI.