Alterations in NMDA receptors in a rat model of cortical dysplasia
Alterations in NMDA receptors in a rat model of cortical dysplasia
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DOI：
10.1152/jn.2000.83.1.315
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发表时间：
2000-01-01
影响因子：
2.5
通讯作者：
Hablitz, JJ
中科院分区：
文献类型：
--
作者：
Defazio, RA;Hablitz, JJ
最近的研究表明 N-甲基-D-天冬氨酸受体 (NMDAR) 在癫痫中发挥着重要作用。 NMDAR 还被证明在与多种人类癫痫动物模型相关的过度兴奋中发挥着关键作用。利用脑切片中的全细胞电压钳记录，我们研究了新皮质小回的冻结损伤模型中诱发的阵发性放电。癫痫样放电的电压依赖性表明这些阵发性事件是由兴奋性和抑制性输入的复杂模式产生的。我们研究了 NMDAR 拮抗剂 D-2-氨基-5-磷酸戊酸 (APV) 和 NMDA 受体亚基 2B (NR2B) 选择性拮抗剂艾芬地尔对病变动物脑切片中诱发癫痫样放电的阈值、峰值幅度和面积的影响。两种化合物始终提高诱发放电的阈值，但对放电峰值和幅度影响不大。为了与未损伤的皮质进行比较，我们检查了艾芬地尔对 2 μM 荷包牡丹碱存在下诱发的癫痫样放电的影响（部分去抑制）。在来自未病变皮质的切片中，10μM艾芬地尔对阈值几乎没有影响，而经荷包牡丹碱处理的病变皮质中71%的记录显示阈值增加>25%。这些结果表明，含有 NR2B 的受体在冷冻损伤的皮质中功能增强，并可能导致在新皮质小脑回模型中观察到的异常过度兴奋。
Recent studies have demonstrated an important role for the N-methyl-D-aspartate receptor (NMDAR) in epilepsy. NMDARs have also been shown to play a critical role in hyperexcitability associated with several animal models of human epilepsy. Using whole-cell voltage clamp recordings in brain slices, we studied evoked paroxysmal discharges in the freeze-lesion model of neocortical microgyria. The voltage dependence of epileptiform discharges indicated that these paroxysmal events were produced by a complex pattern of excitatory and inhibitory inputs. We examined the effect of the NMDAR antagonist D-2-amino-5-phosphopentanoic acid (APV) and the NMDA receptor subunit type 2B (NR2B)-selective antagonist ifenprodil on the threshold, peak amplitude, and area of evoked epileptiform discharges in brain slices from lesioned animals. Both compounds consistently raised the threshold for evoking the discharge but had modest effects on the discharge peak and amplitude. For comparison with nonlesioned cortex, we examined the effects of ifenprodil on the epileptiform discharge evoked in the presence of 2 mu M bicuculline (partial disinhibition). In slices from nonlesioned cortex, 10 mu M ifenprodil had little effect on the threshold whereas 71% of the recordings in bicuculline-treated lesioned cortex showed a >25% increase in threshold. These results suggest that NR2B-containing receptors are functionally enhanced in freeze-lesioned cortex and may contribute to the abnormal hyperexcitability observed in this model of neocortical microgyria.