Mechanism of FTY720 on neural function improvement of rats with traumatic brain injury

Abstract

Objective To investigate the effect of FTY720 on neurological function in rats with traumatic brain injury and the related mechanism. Methods A total of 60 rats were randomly divided to the sham-operation group, model group and treatment group, 20 rats in each group. Modified Feeney free fall injury device was used to build rat craniocerebral injury model. Rats in the treatment group were administrated intraperitoneally with 1 mg/kg FTY720. Rats in the sham-operation group and model group were given 1 ml normal saline by intraperitoneal injection. After 24 hours, 10 rats in each group were sacrifice and their hippocampus tissues were used to determine the expression of nuclear factor-kappa B and microglial OX-42 by Western blotting and immunohistochemistry respectively. Additionally, the forelimb-placement test, balance test and modified neurological severity scores were used to assess the neurological function in each group. Results The expression of nuclear factor-kappa B (F=95.962, P<0.001) and microglial OX-42 (F=108.853, P<0.001) were all showed significant differences among the three groups, and were higher in the model group than those in the sham-operation group and treatment group (all P<0.05). Meanwhile, the forelimb-placement test [(7.0 ± 0.7) vs. (6.3 ± 0.5), (5.9 ± 0.7) vs. (5.0 ± 0.8), (4.9 ± 1.0) vs. (3.8 ± 0.8), (3.7 ± 1.1) vs. (2.3 ± 0.7); t=2.689, 2.586, 2.741, 3.525, P=0.015, 0.019, 0.013, 0.002], balance test [(4.3 ± 0.7) vs. (3.6 ± 0.7), (3.5 ± 1.1) vs. (2.6 ± 0.7), (2.9 ± 0.9) vs. (1.9 ± 0.7), (2.5 ± 0.7) vs. (1.8 ± 0.6); t=2.278, 2.212, 2.762, 2.333, P=0.035, 0.040, 0.013, 0.031] and modified neurological severity scores [(10.1 ± 1.0) vs. (8.7 ± 1.6), (8.8 ± 0.8) vs. (7.5 ± 1.5), (7.3 ± 1.0) vs. (5.6 ± 1.3), (5.7 ± 1.3) vs. (4.1 ± 1.4); t=2.385, 2.414, 3.400, 2.726, P=0.028, 0.027, 0.003, 0.014] on 7, 14, 21, 28 d after operation in the model group were higher as compared with the treatment group. Conclusion FTY720 could markedly improve the neurological function of rats with trauma brain injury and its mechanism might be related to the inhibition of FTY720 on central nervous system inflammation. Key words: Craniocerebral trauma; Rat; FTY720; Neurological function