Neuroprotective effect of erythropoiet in treatment of traumatic brain injury in rats

Objective To evaluate the neuroprotective effects of erythropoiet (EPO) for traumatic brain injury (TBI) in rats and investigate the possible role of endoplasmic reticullum stress response and Caspase-12-induced apoptosis. Methods According to the random number table, 140 male Sprague-Dawley rats were divided into sham injury group, sham injury plus EPO group, TBI group and TBI plus EPO group, with 35 rats per group. TBI was induced by a fluid percussion device. EPO (5 000 U/kg in saline) was administered intraperitoneally at 6 hours after injury. The rate of TUNEL positive cells in injured cortex were measured to evaluate cell apoptosis status. Neurological function was assessed at days 1, 4, 7, 21, 28 and 35 after intervention using a modified neurological severity score (mNSS). At 24 hours after injury, the expressions of Caspase-12 in injured cortex and C/EBP-homologous protein (CHOP) which was the symbol of ERS response were measured by Western blot and immunofluorescent staining to assess the changes of ERS response after TBI and EPO treatment. Results TUNEL-positive staining cell density was significantly increased by (30.3±2.3)% in the injured cortex 24 hours after injury (P<0.01). Compared with TBI group, TBI plus EPO group had a significant decrease of the positive rate of TUNEL cells [ (14.6±1.5)%] (P<0.01). Compared with TBI group, mNSS score significantly was decreased in TBI plus EPO group at 7-35 days after injury (P<0.05). At 24 hours after injury, the results of Western blot showed that the expression levels of Caspase-12 and CHOP in the injured cortex in TBI group were higher than those in sham group, but that in TBI plus EPO group was lower than those in TBI group (P<0.01). At 24 hours after injury, the results of immunofluorescent staining showed the rates of Caspase-12 and CHOP positive cells in the injured cortex in TBI group were higher than sham group (P<0.01). But the rates of Caspase-12 and CHOP positive cells in TBI plus EPO group was lower than that in TBI Group (P<0.01). Conclusion Exogenous EPO has significant neuroprotective effects on TBI rats. EPO may exert its neuroproective effects through suppression of ERS response and inhibition of Caspase-12-induced apoptosis. Key words: Brain injuries; Erythropoietin; Endoplasmic reticulum stress