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

Abstract

Aims: This study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO₂ in a kainic acid (KA) rat model.

Main methods: Four-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 findings: Carbogen increased the onset latency of seizure (KA+air group, 26.12±2.11min; KA+carbogen group 43.65±2.78min, 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).

Significance: Carbogen containing 5% CO₂ decreased seizures by reducing cortical pH, by increasing GABA release, and by affecting electrical activity of the brain.

Keywords: Carbogen; Mechanism; Rat; Seizure; pH.