Date of Award

9-28-2010

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Hal Blumenfeld

Abstract

REMOTE EFFECTS OF FOCAL HIPPOCAMPAL SEIZURES ON THE RAT NEOCORTEX. Peter K. Mansuripur, Dario J. Englot, Asht M. Mishra, Peter Herman, Fahmeed Hyder, and Hal Blumenfeld. Department of Neurology, Yale University, School of Medicine, New Haven, CT. The goal of this study is to establish an animal model of frontal lobe slow-wave activity during complex partial hippocampal seizures, to characterize this activity in terms of its behavioral, neuronal and metabolic activity, and to compare it to secondarily-generalized seizures as well as to the sleeping and anesthetized states. We hypothesize that such slowing does not represent direct spread of seizure activity, but rather a distinct long-range effect similar to sleep or anesthesia. Spontaneous seizures were recorded in awake-behaving Sprague-Dawley rats via intracranial EEG and video after pilocarpine-induced status epilepticus. Blood flow and fMRI measurements were made during stimulus-induced acute seizures under light ketamine/xylazine anesthesia. Neocortical slow-wave activity (1-3 Hz) was observed during a subset of both spontaneous and stimulated seizures; in spontaneous seizures, it was associated with behavioral mildness (p<0.01), in contrast to the convulsive secondarily generalized seizures. Partial seizures were marked on fMRI by signal increases in the hippocampus, thalamus and septum, but decreases in the orbitofrontal, cingulated, and retrosplenial cortices; generalized seizures were marked by increases in all of these regions. Using this data and blood flow measurements, the calculated oxidative metabolism increased in the hippocampus but decreased in the orbitofrontal cortex during partial seizures, whereas it increased in both during generalized seizures. These findings suggest that neocortical slowing represents a distinct phenomenon from direct spread of seizure activity, and may be responsible for the loss of consciousness during partial seizures.

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