Pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats

Abstract

ABSTRACT Primary Objective The primary objective of this study was to explore the pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats. Research Design Weight drop model of traumatic brain injury. Methods and Procedures After TBI, the animals were treated with doxycycline (50 and 100 mg/kg; p.o), tocopherol (5 and 10 mg/kg; p.o) alone and in combination as doxycycline and tocopherol (50 and 10 mg/kg; p.o) from 1st day to 28th day. The behavioral parameters were performed on a weekly basis from 1st day to 28th day. On 29th day, animals were sacrificed and striatum and cortex were homogenized for the estimation of biochemical (LPO, nitrite, and GSH), neuroinflammatory (IL-6, IL-1β, and TNF-α), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Main Outcomes and Results Induction of TBI had significantly reduced locomotor activity, recognition memory, increased neuroinflammatory markers, and imbalance neurotransmitter levels. The treatment with doxycycline and tocopherol alone and in combination significantly attenuated locomotor activity, memory recognition, reduced neuroinflammation, preserved oxidative balance, and restored the level of neurotransmitters. Conclusions The neuroprotective effect of doxycycline and tocopherol might be due to its anti-inflammatory and free radical scavenging mechanisms. Abbreviations TBI: Traumatic brain injury; Doxy: Doxycycline; Toco: Tocopherol; LPO: Lipid peroxidation; MDA: Malondialdehyde; TNF-α: Tumor necrosis factor-alpha; IL-1b: Interleukin-1 beta; GSH: Glutathione; GABA: gamma-Aminobutyric acid.