Tandon Pushpa, Yang Yili, Stafstrom Carl E, Holmes Gregory L
Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital, Boston, MA 02115, USA.
Brain Res Dev Brain Res. 2002 Jun 30;136(2):145-50. doi: 10.1016/s0165-3806(02)00358-9.
There are significant differences in seizure-induced sequelae between the immature and mature brain. We have previously demonstrated that repeated doses of the chemoconvulsant kainic acid is associated with a progressive increase in severity of seizures in adult animals while in immature rats the opposite occurs; seizure intensity decreases with subsequent doses of kainic acid. Likewise, repeated kainic acid seizures causes severe hippocampal damage in mature rats while in the immature brain serial administration of kainic acid causes no demonstrable cell loss. Here we show that recurrent kainic acid seizures in immature rats are associated with a downregulation of kainate receptor binding. No histological damage was noted in any of the rats exposed to recurrent seizures. Furthermore, when tested for visual-spatial memory immature rats with recurrent kainate seizures did not differ from controls. The downregulation of KA receptors following repeated exposure to KA suggests that the decrease in glutamate receptor density might account in part for the observed lack of neuronal loss and decrease in seizure intensity in these animals.
未成熟大脑和成熟大脑在癫痫发作引发的后遗症方面存在显著差异。我们之前已经证明,重复给予化学惊厥剂海藻酸与成年动物癫痫发作严重程度的逐渐增加有关,而在未成熟大鼠中情况则相反;随着后续海藻酸剂量的增加,癫痫发作强度会降低。同样,重复的海藻酸诱发癫痫会在成熟大鼠中导致严重的海马损伤,而在未成熟大脑中,连续给予海藻酸并不会导致明显的细胞损失。在此我们表明,未成熟大鼠反复出现的海藻酸诱发癫痫与海人酸受体结合的下调有关。在任何经历反复癫痫发作的大鼠中均未观察到组织学损伤。此外,在测试视觉空间记忆时,反复出现海藻酸诱发癫痫的未成熟大鼠与对照组没有差异。反复接触海藻酸后海人酸受体的下调表明,谷氨酸受体密度的降低可能部分解释了在这些动物中观察到的神经元损失缺乏和癫痫发作强度降低的现象。