Effects Of Recurrent Neonatal Seizures On Expression Of Adrenocorticoid Receptor In The Rat Hippocampus

Objective: To investigate the effects of flurothyl-induced neonatal recurrent seizures on adrenocorticoid receptor (ACR) expression in developing rat hippocampus, and to discuss the relationship between these receptors and developing brain injury.Methods: 80 of postnatal 7d (PN-7d) Sprague-Dawley rats were divided randomly into two groups: the control group and the seizure group. Seizures were induced by inhalant flurothyl daily in six consecutive days. The brains were sampled on 1d, 3d, 7d, 30d and 60d after seizures. The expressions of minerocorticoid receptor and glucocorticoid receptor protein in hippocampus were detected by immuno-histochemistry method. On PN61-PN64, rats were tested for spatial memory by using the Morris water maze task.Results On PN-64d, the escape latencies from water maze were significantly longer in the seizure rats than in the control rats [(42424.3±35622.0)ms vs (40712.4±29467.6)ms, P=0.001]. On PN-65d, the frequency of crossing target within 120s in water maze were significantly less in the seizure rats than those were in the control rats [(1.2±0.9) vs (3.1±1.3), P＜0.001]. Expression of GR and MR protein at hippocampal CA1-4 region incresed with the developing of brain. On PN-8d, GR have expressed at hippocampal CA1-4 region ,and increased smoothly in one month (CA1 region: F=16.247, P＜0.05; CA2 region: F=52.140, P＜0.05; CA3/4 region: F=23.694, P＜0.05).There were no difference in GR protein expressions between PN-37d and PN-67do In contrast to GR,MR protein expressed at hippocampal CA1-4 region with high levels on PN-8d, expressions of MR protein levels on PN-10d were higher than those on PN-8d (CA1 region: F=4.664, P＜0.05; CA2 region: F=6.751, P＜0.05; CA3/4 region: F=19.241, P＜0.05).MR prtein expessed similar on PN-14d,PN-37d and PN-67d.Compared to the control rats, the expressions of glucocorticoid receptor (GR) and minerocorticoid receptor (MR) protein decreased significantly in the seizure rat CA1-4 region at 1d, 3d, 7d, 30d, and 60d after seizures (P＜0.05). Expression of GR and MR protein in the dentate gyrus(DG) have the similar patterns with hippocampal CA1-4 region(GR: F=107.635, P＜0.05; MR: F=20.836, P＜0.05). Compared to the control rats, the expression of GR protein decreased significantly in DG of seizure rat at 1d, 3d, and 7d after seizures (P＜0.05). There were no difference in GR protein expressions between the two groups at 30d and 60d after seizures (P＞0.05). The expression of MR protein decreased significantly in seizure rat DGs at 1d, 3d, 7d, and 30d after seizure than in control rat DGs (P＜0.05), while the expressions of MR protein were similar in DG between the two groups at 60d after seizures (P＞0.05)Conclusions Recurrent seizures in neonatal rats modify GR and MR expressions in the hippocampusof rats, and cause long-term cognitive deficit. This phenomenon raised the possibility that abnormal GR and MR expression might play an important role in acute brain injury and long-term cognitive deficit induced by early life recurrent seizures.