To investigate the effects and mechanisms of glutamine(Gln) supplementation on oxidative stress, autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats.

TBI animal models were established using Feeney's method. Eighty SD rats were randomly divided into 4 groups: sham operation group (group Sham), Sham + glutamine supplementation group (group Sham+ GLN), traumatic brain injury group (group TBI), and TBI + glutamine supplementation group (group TBI+ GLN). We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1, 3, 7 and 14 after TBI. The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining. The expression of reactive oxygen species (ROS) was tested by ROS kits. Oxidative stress and autophagy related cytokines (HO-1, NQO1, Nrf2, LC3-Ⅱ and Beclin-1) were tested with Western blotting.

Compared with the TBI group, the neurological function was improved[(9.79±0.43)vs.(8.43±0.30), F=6.775, P=0.010] and the apoptosis rate decreased(19.88% ±1.60% vs. 15.35% ±1.28%, P=0.013) in the TBI+ GLN group after 7-day treatment. Compared with the Sham group, the protein expression of ROS increased(P=0.000), and the expression of anti-oxidative stress factors (HO-1, NQO1) and Nrf2 pathway significantly decreased in the TBI group. After glutamine supplementation was given, the expression of ROS decreased and the expressions of HO-1 and NQO1 increased. The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2, LC3-Ⅱ and Beclin-1 increasing.

Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI, thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response, activating Nrf2 pathway and autophagy response.

Traumatic brain injury; Glutamine; Oxidative stress; Nrf2 pathway; Autophagy