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


ABSTRACT: 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.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.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).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.

SUBMITTER: Tschuluun N 

PROVIDER: S-EPMC3230777 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Tschuluun Naranzogt N   Jürgen Wenzel H H   Doisy Emily T ET   Schwartzkroin Philip A PA  

Epilepsia 20110920 12


<h4>Purpose</h4>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.<h4>Methods</h4>Electrophysiologic methods were used to examine the activity of the M  ...[more]

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