Hypercapnia-induced brain acidosis: Effects and putative mechanisms on acute kainate induced seizures.
OBJECTIVE
This study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO2in a kainic acid (KA) rat model.


METHODS
Four-week-old Sprague-Dawley rats were divided into four groups: control, carbogen, KA+air, and KA+carbogen. Carbogen containing 5% CO2was 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.


RESULTS
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).


CONCLUSIONS
Carbogen containing 5% CO2decreased seizures by reducing cortical pH, by increasing GABA release, and by affecting electrical activity of the brain.
Department of Pediatrics, Chinese PLA General Hospital, Beijing 100853, China.
Xiu-Yu
XY
Shi
Department of Pediatrics, Chinese PLA General Hospital, Beijing 100853, China.
Lin-Yan
LY
Hu
Department of Pediatrics, Chinese PLA General Hospital, Beijing 100853, China.
Meng-Jia
MJ
Liu
Department of Pediatrics, Chinese PLA General Hospital, Beijing 100853, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100000, China. Electronic address: zouliping21@hotmail.com.
Li-Ping
LP
Zou
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology*; D007608:Kainic Acid / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
D000927:Anticonvulsants; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen; D007608:Kainic Acid
Carbogen; Mechanism; Rat; Seizure; pH