Hypercapnia-induced brain acidosis: Effects and putative mechanisms on acute kainate induced seizures

•Carbogen decreased KA-induced seizures.•KA and carbogen produced a synergistic effect, further reducing cortical pH.•Carbogen reduced glutamate release and increased GABA release.•Carbogen reduced hippocampal and cortical activity.

AimsThis study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO2 in a kainic acid (KA) rat model.Main methodsFour-week-old Sprague-Dawley rats were divided into four groups: control, carbogen, KA + air, and KA + carbogen. Carbogen containing 5% CO2 was applied immediately after KA injection, and cortical pH was recorded. High-performance liquid chromatography was used to detect the release of γ-aminobutyric acid (GABA) and glutamate. We used electrophysiology to measure cortical and hippocampal activities.Key findingsCarbogen increased the onset latency of seizure (KA + air group, 26.12 ± 2.11 min; KA + carbogen group 43.65 ± 2.78 min, P < 0.001) and reduced the frequency of seizures (KA + air group, 12.50 ± 1.77; KA + carbogen group, 5.63 ± 1.59, P < 0.001). Carbogen inhalation could reduce cortical pH (KA + air group, 7.04 ± 0.04; KA + carbogen group, 6.82 ± 0.03, P < 0.001). After carbogen inhalation, the levels of excitatory amino acid glutamate decreased (595.90 ± 7.51 in KA + air group vs. 467.95 ± 4.82 in KA + carbogen s group, P < 0.001), whereas GABA increased significantly (158.30 ± 5.05 in KA + air group vs. 216.62 ± 5.59 in KA + carbogen, P < 0.05). Carbogen reduced both electrohippocampalogram (119.57 ± 2.83 in KA + air group vs. 107.48 ± 2.95 in KA + carbogen group, P < 0.01) and electrocorticogram (130.74 ± 2.48 in KA + air group vs. 115.35 ± 2.11 in KA + carbogen group, P < 0.01).SignificanceCarbogen containing 5% CO2 decreased seizures by reducing cortical pH, by increasing GABA release, and by affecting electrical activity of the brain.