Abstracts

Photothrombotic brain infarction resusts in altered expression of cortical GABA[sub]A[/sub] receptors in rats. To better understand potential time-dependent changes in GABA[sub]A[/sub] receptor [alpha][sub]1 [/sub]subunit mRNA expression associated with epileptogenesis, we quantified the mRNA levels at 1, 3, 7, and 30 days after photothrombosis. Photothrombosis was performed on 3 mo old Sprague-Dawley rats. Lesioned (n = 32) and sham-operated (n=32) rats were sacrificed at 1, 3, 7, and 30 days post-lesioning (lesioned, n = 4, and sham-operated, n = 4, at each time point). Na[iuml]ve controls (n = 6) were used for comparison. Quantitative competitive RT-PCR was performed on cortical tissue samples taken from two concentric arcs of tissue surrounding the lesion (L1 and L2), and also from homotopic cortex (R1 and R2). Subunit mRNA levels were expressed as mean [plusmn] SEM. Unpaired [italic]t-[/italic]tests (p[lt]0.01) compared mean mRNA expressed in areas in lesioned rats with the corresponding mean mRNA values of sham-operated rats. One-way ANOVA testing (p[lt]0.01), with Bonferroni multiple comparisons post-testing (p[lt]0.01) was used to compare mean mRNA expression at different timepoints for each area of ipsilateral or contralateral hemispheres in lesioned and sham-operated cohorts. There was no significant difference in [alpha][sub]1 [/sub]subunit mRNA expression for lesioned vs. sham-operated animals at 1 and 3 days (p [lt] 0.01; unpaired [italic]t[/italic]-test). A significant decrease in mRNA at 7 days in lesioned animals was determined for L1 (41.2 [plusmn] 7.4 pg, p = 0.0093), R1 (39.0 [plusmn] 4.9 pg, p = 0.0062), and R2 (31.2 [plusmn] 3.4 pg, p [lt] 0.0001) cortical areas compared with the corresponding areas of sham-operated animals. In contrast, mRNA at 30 days increased in lesioned animals for L1 (197.8 [plusmn] 25.6 pg, p = 0.0019) and L2 (258.4 [plusmn] 26.5 pg, p = 0.0001) compared with sham-operated animals. One-way ANOVA (p [lt] 0.01) of mean mRNA at 30 days in lesioned animals indicated that L1 (197.8 [plusmn] 25.6 pg), L2 (258.4 [plusmn] 26.5 pg), R1 (153.6 [plusmn] 13.2 pg), and R2 (141.4 [plusmn] 16.0 pg) increased significantly compared to all other time points (p [lt] 0.01); mean mRNA expression at day 7 for R1 (39.0 [plusmn] 4.9 pg) was decreased compared with R1 (47.0 [plusmn] 5.7 pg) at 1 day (p [lt] 0.01). Expression in sham-operated animals at 30 days for R1 (115.7 [plusmn] 7.5 pg) was increased compared with 3 and 7 days (64.7 [plusmn] 6.6 pg and 80.5 [plusmn] 8.5 pg), respectively. Na[iuml]ve animals were not included in statistical comparisons. GABA[sub]A [/sub]receptor [alpha][sub]1[/sub] subunit mRNA expression was unchanged at 1 and 3 days, reduced bilaterally at 7 days, and increased bilaterally at 30 days. Changes in GABA[sub]A [/sub]receptor [alpha][sub]1[/sub] subunit mRNA expression may coincide with the development of poststroke epileptogenesis demonstrated previously in this model. (Supported by American Heart Association Award 0151398U to KMK.)