ABSTRACT
Objective To investigate the effects and mechanisms of Glutamine (Gln) supplementation on neurobehavioral outcome,neuronal apoptosis,microglia polarization,and neuroinflammatory response after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Sixty Wistar rats were randomly divided into three groups:control group (Con),traumatic brain injury group (TBI),and glutamine supplementation group (TBI+Gln).We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1,3,7 and 14 after TBI.Apoptotic neurons were determined by Nissl staining.The microglia polarization relatived protein (Iba-1,CD16,CD86) expressions in TBI cerebral cortices were determined by immunohistochemistry staining and western blotting,respectively.While,the serum levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1 and interferon (IFN)-γ were tested by enzyme linked immunosorbent Assay (ELISA).Results Compared with the Con group,the levels of neurobehavioral outcome,neurons apoptosis,microglia polarization and neuroinflammatory factors were significantly increased in the other two groups (P=0.00).Compared with the TBl group,glutamin supplementation improvedneurobehavioral outcome [7 d:(10.74±0.25) points vs.(8.94±0.24) points,P=0.01;14 d:(8.77± 0.16) points vs.(7.43±0.13) points,P=0.03].Meanwhile,glutamin supplementation suppressed the apoptotic rates of neurons [3d:(80.18±8.38)％ vs.(65.47±7.02)％,P=0.01;7 d:(58.90±6.12)％ vs.(42.73±4.88)％,P=0.01;14d:(39.56±2.95)％vs.(31.12±3.16)％,P=0.01],inhibited protein expressions of Iba-1 and CD16,and increased the protein expression of CD86,which promoted the phenotypic shift of microglia from M1 to M2 phenotype,inhibited microglial activation,and thus reduced TBI-induced neuroinflammatory factors [TNF-α:(125.42 ± 12.81) pg/ml vs.(74.36 ± 9.25) pg/ml,P =0.01;IL-1:(69.04±8.48) pg/ml vs.(34.73±3.92) pg/ml,P=0.01;TNF-α:(89.75±9.40) pg/ml vs.(45.62±6.64) pg/ml,P=0.02].Conclusion Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI,possibly mediated by promoting the phenotypic shift of microglia from M1 to M2 phenotype and thus reducing TBI-induced neuroinflammatory factors.