Febrile seizures of rats during brain development enhance the future brain injury of seizures

Abstract

Objective Seizure is one of the most common neurological diseases, with the highest incidence during the first year of life. It is unclear about the effect of the seizure during brain development, especially the febrile convulsion. Therefore, the authors compared the brain injury of the kainate-induced seizure in adult rats between the rats with (group FK) and without febrile (group K) convulsion in early development time, and intend to determine whether and how the seizure during the brain development has the long term effect on the brain. Methods The febrile seizure model was established in the rats of postnatal 15 days by using hot water bath. The induced seizures lasted 1-2 minutes each time, once a day for 5 consecutive days. At the 55th day of postnatal, kainate was used to induce the rats (group FK) convulsion again ( hit model). The rats of group K only have 1 kainate-induced seizure during the adulthood (postnatal 55 days), and the rats of group F only have febrile seizures during the development. After the second time seizure, the seizure latent time, learning, memory and behavior changes were observed; meanwhile the mossy fiber sprouting in the hippocampus by Timm staining and apoptosis of neurons in the hippocampus by TUNEL were defined. Results After the second time seizure, the rats in both group FK and group K presented markedly abnormal behavior, such as irritability, wild running and jumping, and transient spontaneous seizure, but there was no difference in the latent time of seizure between the two groups [(40±6)s vs. (46±6)s, P>0.05]. The abnormal behavior gradually diminished in rats of group K after 5 days, while the abnormal behavior lasted until the sacrifice at the 65th day in rats of group FK. In Morris water maze test during the 60 to 65 days, the average searching platform latency (SPL) was significantly longer in rats of group FK [(24.3±2.7)s], group K [(16.9±3.3)s] (P<0.01) than rats of group F[(6.0±2.0)s], group C [(5.5±2.3)s, P<0.01], there was also significant difference between group FK and group K (P<0.01). No significant difference was seen between the rats of group F and group C. Mossy fiber sprouting has been found in supragranular layer of dentate in the rats of all groups, and increased markedly in rats of group FK [M=2.83] and group K [M=2.33] when compared with those in rats of group F [M=0.25, P<0.01]. The difference between group FK and group K was also significant (P<0.01). The apoptosis neurons in hippocampus in the rats of group FK and group K increased markedly [M=21.9, 14.5] compared to the rats of group F [M=0.7, P<0.01] 3 days after seizure, there was also significant difference between group FK and group K (P<0.01). Conclusion Although neuron apoptosis hasn′t been found in hippocampus during febrile seizures after 15-19 postnatal days, apoptosis neurons in hippocampus after serzure significantly increased in adult rats with the febrile seizure experience during the development, as well as mossy fibers sprouting in hippocampus. The rats with early seizures also presented marked defect of the space learning, memory and behavior. Therefore, seizures during the development might not induce marked neuron pathological injury, but seizures during the development increased the sensitivity of neuron injury to the later seizures during adulthood. Key words: Rets; Convulsions, febrile; Brain damage, chronic; Heat