Topiramate

Ketamine/xylazine was purchased from Sigma-Aldrich. ¹⁴C-sucrose and optiphase supermix scintillation cocktail were purchased from PerkinElmer. ³H-Sumatriptan was purchased from American Radiolabeled Chemicals Inc. Sumatriptan was generously donated by the Porreca Lab (University of Arizona; source: Abmole Bioscience). Topiramate was purchased from Cayman Chemical. TS-2 tissue solubilizer was purchased from Research Products International. EDTA-free complete protease inhibitors were purchased from Roche. The Coomassie Plus Better Bradford Assay kit was purchased from Thermo Scientific. XT sample buffer, XT reducing agent, Precision Plus dual color prestained molecular weight markers, and TGX criterion gels were purchased from Bio-Rad. Primary antibodies used for Western blotting (WB) include the following: claudin-5 [Invitrogen (Thermo Fisher), catalog #4C3C2, 1:500], occludin [Invitrogen (Thermo Fisher), catalog #OC-3F10, 1:1000], and α-tubulin (Cell Signaling, catalog #DM1A, 1:5000). Secondary antibodies for WB were purchased from Cell Signaling Technology and used at a 1:20,000 dilution. All other chemicals were purchased from Sigma-Aldrich.

Rats implanted with ventral hippocampal electrodes and dorsal hippocampal optodes were used in these studies. Rats were reused for several drug experiments allowing at least two days between drug treatments. Celecoxib, SC-560, ibuprofen, chelerythrine chloride, milrinone, sildenafil, SKA-31, CAY-10526, seratrodast, ozagrel, paxilline, 2-APB, levetiracetam, and topiramate were obtained from Cayman Chemicals (Ann Arbor, MI). Acetaminophen, nifedipine, bumetanide, ethosuximide, phenytoin, and valproic acid were obtained from Sigma-Aldrich. Lamotrigine was obtained from SelleckChem (Houston, TX). Fasudil was obtained from LC laboratories (Woburn, MA) and phenobarbital was obtained from Strathcona Prescription Center (Canada). Lipophilic drugs were dissolved in 100% DMSO, while hydrophilic drugs were dissolved in saline and injected 30 min prior to seizure induction. The seizure duration and severity of hypoxia (area below 10 mmHg) were compared across kindle (seizure without injection), vehicle-, and drug-treated groups using a within-subject ANOVA and follow-up t-test between vehicle- and drug-treated groups.