Neuroprotective Effects of Taxifolin Against Weight Drop Induced Traumatic Brain Injury in Rats

Abstract

Background and Aim: ABSTRACT Mechanical injury to the brain due to penetration or hitting of the head is referred to as traumatic brain injury (TBI). TBI causes a very high mortality and morbidity rate. TBI damages the brain tissue at the structural and molecular level causing Blood-Brain Barrier disruption, neuroinflammation, neurodegeneration, oxidative stress, and axonal disconnection. Taxifolin is reported to have anti-inflammatory, anti-oxidant properties. Thus, this study deals with the investigation of the neuroprotective function of Taxifolin in TBI with the help of the weight drop method in rats. Experimental Method: Wistar rats of either sex, weighing 250-300gm were utilized in this study. The animals were assigned into four groups; control and TBI groups pre-treated with the vehicle, and two TBI groups pre-treated with different doses of Taxifolin (2 and 5 mg/kg/day, i.p., five consecutive days). Except for the control, all other groups were subjected to TBI using Marmarou's weight-drop method. 24 h after TBI, the locomotor function was evaluated. Lastly, animals were sacrificed and the estimation of lipid peroxidation, nitric oxide, and myeloperoxidase in brain tissue, blood-brain barrier (BBB) integrity, brain water content (brain oedema), and TLR4 expression in the brain tissue was performed. Results: From the following study, it was found that Taxifolin is therapeutically effective in pre- treatment therapy of TBI. Taxifolin improved the motor coordination activity in the brain measured through beam walking test in TBI-induced rats. Taxifolin was also able to conserve the BBB disruption, which leads to a decrease in edema formation. Taxifolin also ameliorated lipid peroxidation, inflammatory damage, and neuro-inflammation. By using the TLR4-ELISA kit, it was confirmed that TLR4 contributes to secondary damage, and its expression is attenuated by Taxifolin effectively in TBI-exposed animals. Conclusion: Taxifolin acts as a potential neuroprotective agent. It reduces the damage caused by secondary injury in TBI affected brain. Taxifolin acts on TLR4 and decreases its expression thus ameliorating BBB disruption, edema formation, neuroinflammation, neurodegeneration, oxidative stress.