Comparison of efficacy of adrenocorticotrophic hormone and methylprednisolone on rat models of infantile spasm

Abstract

Objective To compare the efficacy of adrenocorticotrophic hormone(ACTH) and methylprednisolone on the rat models of infantile spasms(IS). Methods The SD rats on postnatal 10 day (P10) were divided into blank group (n=18), control group (n=18) and model group (n=110) according to the random number table method.The rats of model group were prepared by adopting prenatal stress exposure and N- methyl -D aspartate (NMDA) injection.In the model group, after inducing epileptic seizures, the rats were divided into different groups (18 rats in each group) according to the random number table method as following: model group Ⅰ (subcutaneous injection of ACTH, 50 IU/kg, at P10: 1400, 2100; P11, P12: 700, 1400, 2100; P13: 700), model group Ⅱ(subcutaneous injection of 9 g/L saline), model group Ⅲ (intraperitoneal injection of methylprednisolone, 60 mg/kg, at P11, P12, P13: 900, once per day), model group Ⅳ (intraperitoneal injection of 9 g/L saline) and model group Ⅴ (positive control group, with no drug or saline injection). Three days later, epilepsy was induced again, and the rats of model group were intraperitoneally injected with NMDA (12 mg/kg) at P13(1000). The rats of control group were injected intraperitoneally with same volume of 9 g/L saline, but the rats of blank group were not treated.Behaviors of rats with epilepsy seizures were observed and epilepsy scores were given.The expression of corticotropin-releasing hormone (CRH) in the hypothalamus of each group was detected by using immunohistochemistry and fluorescence quantitative polymerase chain reaction.The learning and memorizing capacity of the rats were measured by Y-maze experiment. Results There was no death in the model group after the onset of seizure.In the model group Ⅰ, 13 cases were attacked(72.22%), and 14 cases were attacked in the model group Ⅲ(78.78%). The level of attack was decreased.The buckling state was not observed in model group and Ⅲ, but the latency period of epilepsy was prolonged and the epilepsy scores were significantly decreased.There were no significant differences of onset latency [(2 369.38±628.70) s vs.(1 922.93±462.36) s] and epilepsy score[(2.15±1.14) scores vs.(2.07±0.83) scores] between the 2 groups (all P>0.005). The rats of model group Ⅱ, Ⅳ, Ⅴ were all attacked completely and presented buckling state.There was no onset or death in blank group and control group.The number of CRH positive cells and CRH mRNA relative expression of each model group were higher than those in the blank group and control group.The number of CRH positive cells and CRH mRNA expression of model group Ⅰ and Ⅲ were lower than those in model group Ⅱ, Ⅳ and Ⅴ, and the differences were significant (all P 0.002 4). No significant difference was found between blank group and control group, or among model group Ⅱ, Ⅳ and Ⅴ (all P>0.002 4). There were no significant differences in the learning capacity among all groups (F=2.196, P>0.002 4). The correct response rate after 24 hours of the model group was lower than the blank group and control group, and ACTH and methylprednisolone pretreatment did not influence the memorizing capacity (P>0.002 4). Conclusion The effect of pretreatment of ACTH is similar to that of methylprednisolone in the rat model of IS. Key words: Infantile spasm; Adrenocorticotrophic hormone; Methylprednisolone; Rats model; Corticotropin-releasing hormone