Effect of glucocorticoids therapy on mortality and secondary brain injury in rats after traumatic brain injury

Objective To investigate the effect of glucocorticoids of different dosages on mortality and hippocampal neuron apoptosis in rats after traumatic brain injury (TBI).Methods All the adult male Wistar rats were allocated into normal control group,dexamethasone (DXM) treatment group,methylprednisolone (MP) treatment group,injury control group,low-dose DXM treatment group,moderate-dose DXM treatment group,high-dose DXM treatment group,low-dose MP treatment group,moderate-dose MP treatment group,and high-dose MP treatment group (n=22).Rats in the later seven groups (the injuried groups) accepted fluid percussion injury to induce TBI models,and then,treatments were given.The injury severity was evaluated with modified Neurological Severity Scale 24 h after injury.The number ofhippocampal neuron apoptosis was examined using TUNEL after 24 and 48 h,and 7 and 14 d of injury.The mortality of rats in each group was also observed during a 14-day-follow-up period.The changes of brains,pituitaries,hearts and lungs in the dead rats were examined by H.E.staining.Results No significant difference on the scores of modified Neurological Severity Scale was noted in the injuried groups 24 h after the injury (P＞0.05).The hippocampal neuron apoptosis began to appear 24 h after inju~,peaked at 48 h,and declined in 7 to 14 d.At 48 h after injury,the number of hippocampal neuron apoptosis in high-dose DXM treatment and high-dose MP treatment groups was significantly higher than that in the injury control group (P＜0.05).The mortality of rats in high-dose DXM treatment and high-dose MP treatment was significantly higher than that in the injury control group (P＜0.05).The autopsy of dead rats in each group revealed various degrees of interstitial pneumonia and hypophysial congestion in rats receiving high-dose glucocorticoids.Conclusion TBI could induce hippocampal neuron apoptosis,and early administration of high-dose glucocorticoids aggravates the apoptosis and increases the mortality,for which interstitial pneumonia and hypophysial congestion would account. Key words: Traumatic brian injury;  Glucocorticoids;  Secondary brain injury;  Apoptosis; Interstitial pneumonia;  Pituitary congestion