The Effects Of Bilateral Adrenalectomy And High-dose Adrenocorticotropic Hormone On NMDA-induced Spasm Seizures In Young Wistar Rats

Objectives To demonstrate the relationship between adrenal dysfunction andspasm seizures in young rats, bilateral adrenalectomy (ADX) andN-methyl-D-aspartate (NMDA)-induced rat model studies of infant spasms wereperformed. Material and Methods Wistar rats at p10were used. The animalswere divided into seven groups:1) Control group;2) ACTH group,3) NS group;4) ADX group;5) Sham-ADX group;6) ADX+ACTH group and7)Sham-ADX+ACTH group. The adrenal glands were removed bilaterally inpostnatal10-day-old Wistar rats. Sham operations were performed bymanipulating the rats in the same manner but without removal of the adrenalglands. At24h after bilateral ADX, p11rats received100U/kg ACTH i.p. P11rats of each group received7mg/kg NMDA i.p.30min after ACTHadministration. Hormone levels were determined using [125I] antigen-labeleddouble-antibody RIA kits for corticosterone and ACTH. The oligonucleotide CRHmRNA probe was labeled with digitoxin. For each animal, the relative opticaldensity of CRHmRNA–positive neurons in the hippocampus was measured bycomputer-assisted densitometry. Data were analyzed by independent sample t-testor one-way ANOVA. Results Latency of the ACTH group increased by55%compared with the control group (F=41.75, p <0.05). Latency of the ADX groupdecreased by13%compared with the control group (F=6.269, p <0.05) but thedifference between the control and the Sham-ADX groups was not significant.Latency in the ADX rats increased by28%after ACTH administration (t=4.199,p <0.05). Latency of the Sham-ADX+ACTH group increased significantlycompared with the Sham-ADX group (t=2.420, p <0.05). There was no significant difference between the ADX+ACTH and the Sham-ADX+ACTHgroups (t=1.216, p>0.05). The severity of seizures in the ACTH group decreasedsignificantly compared with the control and the NS groups (F=19.578, p <0.05).After removal of the adrenal glands, the severity of seizures in the ADX groupincreased by18%compared with the control and the Sham-ADX group(F=10.080, p <0.05). The severity of seizures in the ADX+ACTH groupdecreased by34%compared with the ADX group (t=9.244, p <0.05). Theseverity of seizures in the Sham-ADX+ACTH group decreased significantlycompared with those of the Sham-ADX group (t=4.884, p <0.05). Thedifference in severity of seizures between the ADX+ACTH and theSham-ADX+ACTH groups was not significant (t=0.988, p>0.05). ACTHsignificantly relieved NMDA-induced seizures independent of the adrenal glandsin the infant rats. Three hours after ACTH injection, the optical density of CRHmRNA was reduced to62%that of the control value (F=384.643, p <0.05).CRH mRNA expression in ADX rats was significantly elevated compared withthose of Control group. CRH mRNA level in the ADX group was approximately10%greater than in Sham-ADX group (F=30.259, p <0.05). ACTHadministration significantly reversed CRH mRNA overexpression in ADX rats (t=18.467, p <0.05). The level of CRH mRNA was also reduced by ACTHinjection in Sham-ADX rats (t=14.635, p <0.05). CRH mRNA betweenADX+ACTH group and Sham-ADX+ACTH group was not significantly different(t=1.229, p>0.05). Conclusions Adrenal dysfunction exacerbatesNMDA-induced spasm seizures in young rats, which might be related to CRHmRNA expression in the hippocampus. Infants with adrenal diseases may beliable to infant spasms. High-dose ACTH can act as an anticonvulsant byinhibiting CRH mRNA expression in the hippocampus of infant rats.The effect ofACTH on CRH mRNA expression is independent of adrenal corticosteroid.