Protective effects of fingolimod on cognitive function in rats with subarachnoid hemorrhage and its mechanism

Abstract

Objective To investigate the effect of fingolimod on cognitive function in rats with subarachnoid hemorrhage and its mechanism. Methods A total of 96 rats were randomly assigned to the control group, sham-operation group, model group and treatment group, 24 rats in each group. Rats in the control group only received 1 mL 0.9% sodium chloride injection by intraperitoneal injection. The rats in the model group and treatment group were established subarachnoid hemorrhage model via double autologous blood injection into cisterna magna, and rats in the sham-operation group were injected amount of saline twice. Moreover, rats in the treatment group were administrated intraperitoneally with 1 mg/kg fingolimod at 0.5 h before model establishment, and rats in the sham-operation group and model group were given 1 mL 0.9% sodium chloride injection by intraperitoneal injection at the same time. On 8 and 22 d after model establishment, 12 rats from each group were continuously recorded escape latency 5 d by using Morris water maze. The rest rats were sacrificed at 24 h after model establishment. The hippocampus tissues were used to observe the inflammatory cell infiltration and determine the levels of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 by enzyme linked immunosorbent assay. Results The escape latency among the four groups on 8, 9, 10, 11, 12, 22, 23, 24, 25, and 26 d after model establishment were all showed significant differences (F = 171.147, 59.363, 104.145, 91.132, 67.732, 25.580, 21.809, 26.693, 22.254, 24.319; all P < 0.001). The escape latency in the model group and treatment group were longer than those in the control group and sham-operation group, and were longest in the model group (all P < 0.001). Meanwhile, inflammatory cellular infiltration of hippocampus tissues in the model group and treatment group increased. The levels of IL-1β, TNF-α and IL-6 among the four groups also showed significant differences (F = 231.650, 165.281, 158.320; all P < 0.001), and these levels in the model group and treatment group were higher than those in the control group and sham-operation group, and were highest in the model group (all P < 0.001). Conclusion Fingolimod can markedly improve the cognitive function of rats with subarachnoid hemorrhage and its mechanism might be related to the inhibition of fingolimod on central nervous system inflammation. Key words: Fingolimod; Subarachnoid hemorrhage; Cognition; Rat