Abstracts

RATIONALE: Photothrombotic brain infarction can result in altered expression of cortical GABAA receptors and in epileptic seizures in adult rats. We sought to determine whether infarct size and/or epileptic seizures resulted in a differential expression of cortical GABAA receptor [alpha]1, [beta]1, and [gamma]2S subunit mRNA both ipsilateral and contralateral to the lesion. At the end of this activity the participants should be able to discuss photothrombotic brain infarction and the potential role of GABAergic mechanisms in neocortical epileptogenesis.
METHODS: Photothrombosis was performed to create 2-3 mm diameter cortical lesions that extended approximately half-way to (small lesions) or fully to (large lesions) the subcortical-cortical interface. Fourteen young adult male rats were used in these studies: 8 animals underwent photothrombotic brain infarction (3 with small lesions, no epilepsy; 3 with large lesions, no epilepsy; and 2 with large lesions, epilepsy) and 6 animals were used as controls. Animals were monitored for seizure activity using continuous video-EEG monitoring techniques before sacrifice and removal of hemispheric cortices. A reverse transcription-polymerase chain reaction (RT-PCR) was used with internal standards for GABAA receptor subunits to quantitate mRNA expression in cortex ipsilateral (left) and contralateral (right) to the infarct for [alpha]1, [beta]1. and [gamma]2S subunits in nonepileptic animals with small or large infarcts, epileptic animals with large infarcts, and young adult controls. ANOVA and Student[ssquote]s [italic]t[/italic]-test were performed for group comparisons (p[lt]0.05).
RESULTS: Significant alterations in GABAA receptor subunit mRNA expression was seen for [alpha]1 ipsilaterally in animals with large infarcts and epilepsy (increased 284% compared to control; increased 184% compared to contralateral side) and for [beta]1 ipsilaterally in animals with large infarcts and epilepsy (decreased 120% compared to control) and no epilepsy (decreased 152% compared to control). The only other intragroup variation of significance was for [beta]1 in animals with small lesions where mRNA values were different for ipsilateral and contralateral cortices but not different compared to controls.
CONCLUSIONS: These results indicate that GABAA receptor subunit mRNA is differentially expressed in neocortex following photothrombotic brain infarction due to the effects of large cortical infarcts, acute seizures, and/or the epileptic state. Alteration in cortical GABAergic systems following photothrombotic infarction appears to be a complex phenomenon that primarily involves tissue ipsilateral to the lesion. Potential changes in the subunit composition of expressed GABAA receptors could result in altered receptor pharmacological sensitivity and gating kinetics, and decreased postsynaptic inhibition thereby contributing to the mechanisms of poststroke epileptogenesis.
[Supported by: American Heart Association Grant-In-Aid to KMK.]