Abstracts

Rationale: The kindling paradigm is a well-established animal model of temporal lobe epilepsy and is defined as the progressive intensification of brain excitability upon repeated administration of subconvulsive electrical or chemical stimuli that ultimately leads to the establishment of a permanent focus and seizure disorder. To begin to assess long-term gene alteration, independent of acute seizure-related events, we utilized microarray to examine gene expression in the hippocampus of amygdala kindled animals two weeks after reaching fully (permanent) kindled criteria. Methods: Male S-D rats (60 doa) were either kindled using a 1s train of 60 Hz biphasic square wave (200 μAmp peak to peak) administered daily to the basolateral amygdala until fully kindled (4 consecutive stage 5 seizures) or surgically implanted with electrodes but not stimulated (sham control). Microarray gene analysis (Affymetrix) was conducted on hippocampal extracts in 6 control (1 chip/animal) and 6 fully kindled (1 chip/animal) subjects 14 days after the final stage 5 seizure. Out of 31,099 probe sets, those characterized as 'Present' in at least 4 out of 6 replicates were selected in both control and kindled. Genes were then selected that had either >1.25 or <0.8 (1/1.25) fold change relative to control (each kindled value divided by the average from 6 controls). Genes meeting the ± fold change criteria were analyzed further with GeneSpring v. 7.2 (Agilent Technologies, Palo Alto, CA) and group comparisons (control vs kindled) were analyzed using unpaired parametric t-tests with a 5% confidence interval. Results: Results: Among 20,978 “present” genes, 301 genes with >