THE SHORT AND LONG TERM EFFECT OF EARLY-LIFE SEIZURES ON RAT'S BRAIN

Jiang YW, Zhang GJ, Wu XR

Department of Pediatrics, Peking University First Hospital, Beijing 100034

 

Objective: To study the short and long term effect of early-life seizures on rat's brain.

Methods: We use a ¡°two hit¡± rat seizure model, in which systemic kainate or hot water bath was used to induce seizures on 15 postnatal day (P15) and systemic kainate again on 55 postnatal day (P55). We recorded the latent period of seizures during developmental period and adulthood. After the second time seizure, we observe behavior of the rats in all groups, and test memory by Morris water maze; meanwhile we also examine the mossy fiber sprouting in the hippocampus by Timm staining and apoptosis of neurons in the hippocampus and cortex by TUNEL staining.

Results: The latent period of kainate-induced seizure during development is markedly shorter than that of seizures during adulthood, but the mossy fiber sprouting and neuron apoptosis were more severe in latter group. After seizure, there was no difference between rats with seizure on P15 and normal rats without seizure in the average searching platform latencies (SPL) in Morris water maze, but the SPL was significantly longer in rats with seizure on P55 than that in rats with seizure on P15. Compared the rats with and without seizure during early development after the second time seizure, the mossy fiber sprouting and apoptosis of neurons were significantly more severe in the former without reference to seizure type, as well as SPL in water maze. The rats in the former group also presented markedly more severe behavioral problem than that of the rats in the latter group.

Conclusion: Although seizure susceptibility was higher during development than that in adulthood, but the brain injury after seizure was milder in the former. No detectable histologic evidence of brain injury had been found after first kainate-induced seizure or febrile seizure during development, but brain injury, such as neurons apoptosis and mossy fibers sprouting, was significantly more severe in adult rats with seizures during development. It indicated that seizures during development may induce subtle neuron pathological injury to increase susceptibility of the neuron to the harmful effects of seizures later during adulthood.

 
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