Initiation of epileptiform activity in a rat model of periventricular nodular heterotopia

被引:22
作者
Tschuluun, Naranzogt [1 ]
Wenzel, H. Jurrgen [1 ]
Doisy, Emily T. [1 ]
Schwartzkroin, Philip A. [1 ]
机构
[1] Univ Calif Davis, Dept Neurol Surg, Davis, CA 95616 USA
关键词
Bicuculline; Cortical dysplasia; Electrographic seizure episode; Epileptic focus; Hippocampus; Interictal spikes; Neocortex; NEURONAL MIGRATION DISORDERS; PRENATAL METHYLAZOXYMETHANOL TREATMENT; FOCAL CORTICAL DYSPLASIA; FILAMIN-A MUTATIONS; SEIZURE SUSCEPTIBILITY; GENETIC MALFORMATIONS; PYRAMIDAL NEURONS; ANIMAL-MODELS; EPILEPSY; EEG;
D O I
10.1111/j.1528-1167.2011.03264.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Purpose: Periventricular nodular heterotopia (PNH) is, in humans, often associated with difficult-to-control epilepsy. However, there is considerable controversy about the role of the PNH in seizure generation and spread. To study this issue, we have used a rat model in which injection of methylazoxymethanol (MAM) into pregnant rat dams produces offspring with nodular heterotopia-like brain abnormalities. Methods: Electrophysiologic methods were used to examine the activity of the MAM-induced PNH relative to activity in the neighboring hippocampus and overlying neocortex. Recordings were obtained simultaneously from these three structures in slice preparations from MAM-exposed rats and in intact animals. Bath application or systemic injection of bicuculline was used to induce epileptiform activity. Key Findings: In the in vitro slice, epileptiform discharge was generally initiated in hippocampus. In some cases, independent PNH discharge occurred, but the PNH never "led" discharges in hippocampus or neocortex. Intracellular recordings from PNH neurons confirmed that these cells received synaptic drive from both hippocampus and neocortex, and sent axonal projections to these structures-consistent with anatomic observations of biocytin-injected PNH cells. In intact animal preparations, bicuculline injection resulted in epileptiform discharge in all experiments, with a period of ictal-like electrographic activity typically initiated within 2-3 min after drug injection. In almost all animals, the onset of ictus was seen synchronously across PNH, hippocampal, and neocortical electrodes; in a few cases, the PNH electrode (histologically confirmed) did not participate, but in no case was activity initiated in the PNH electrode. Interictal discharge was also synchronized across all three electrodes; again, the PNH never "led" the other two electrodes, and typically followed (onset several milliseconds after hippocampal/neocortical discharge onset). Significance: These results do not support the hypothesis that the PNH lesion is the primary epileptogenic site, since it does not initiate or lead epileptiform activity that subsequently propagates to other brain regions.
引用
收藏
页码:2304 / 2314
页数:11
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