Effects of Carbon Dioxide and Oxygen on Properties of Experimental Seizures in Mice

Abstract

The influence of various concentrations of carbon dioxide and oxygen on the pattern of maximal electroshock seizures (MES), on pentylenetetrazol (Metrazol)-induced seizures, and on recovery time (RT50) from MES has been studied in mice. The major results are summarized as follows: Increasing the concentration of carbon dioxide in 20% oxygen resulted in marked changes in the MES pattern. The duration of the tonic flexor component was increased, and the duration of the tonic extensor component and of the entire tonic phase was decreased; the ratio of flexion to extension was increased markedly. These changes indicate an anticonvulsant effect of carbon dioxide. Carbon dioxide in a concentration of 15.6% protected 50% of mice against a 97% convulsant dose (CD97) of Metrazol. Hypoxia, induced by inhalation of 15 or 10% oxygen, decreased the duration of the tonic flexor component and increased the duration of the tonic extensor component of the MES; the duration of the entire tonic phase was increased; the ratio of flexion to extension was slightly decreased. These changes indicate an excitatory effect of low oxygen concentrations on the brain, under the stated conditions. Hyperoxia, induced by inhalation of 50, 75 or 90% oxygen, in contrast to hypoxia, resulted in effects on MES similar to those produced by inhalation of carbon dioxide. The RT50 was slightly, but not significantly, decreased by hypoxia (15% oxygen), unchanged by hyperoxia (50% oxygen), and markedly increased by an increase in carbon dioxide concentration. Carbon dioxide (5 and 10%) combined with hypoxia (10% oxygen) produced effects on MES pattern and RT50 similar to those produced by carbon dioxide in 20% oxygen.

Respiratory changes with seizures in localization‐related epilepsy: Analysis of periictal hypercapnia and airflow patterns

“…Hypercapnic acidosis may limit seizure discharges in patients with epilepsy and in experimental models of epilepsy (Lennox, 1929; Mitchell & Grubbs, 1956; Woodbury et al, 1956). However, the severe hypoxemia and hypercapnia that occur with some seizures may be sufficient to lead to SUDEP directly or indirectly, for example, by precipitating cardiac arrhythmias.…”

Five percent CO2 is a potent, fast-acting inhalation anticonvulsant

“…The anticonvulsant action of CO 2 was demonstrated as early as 1928 in humans with petit mal epilepsy by the suppression of the characteristic electroencephalography (EEG) spike-wave pattern during administration of carbogen containing 10% CO 2 (Lennox, 1928;Lennox et al, 1936). This finding was extended in several studies on rodent, canine, and nonhuman primate models (Pollock, 1949;Dahlberg-Parrow, 1951;Woodbury et al, 1955;Mitchell & Grubbs, 1956;Woodbury et al, 1958;Meyer et al, 1961;Caspers & Speckmann, 1972;Balestrino & Somjen, 1988;Ziemann et al, 2008), and by observations in psychiatric patients where 15-30% CO 2 prevented electrically induced convulsions . In most of these studies relatively high CO 2 levels (around 10% and above) were used.…”

Stopping Seizures with Carbon Dioxide

“…Although it has been known for more than 80 years that inhalation of an increased concentration of CO 2 may suppress seizures (1, 2), this phenomenon has not been exploited as a clinical treatment. Nonetheless, there is extensive experimental and clinical literature documenting that CO 2 concentrations of 10% and above can block or terminate a variety of seizures in animals and humans (3, 4), including electroshock seizures in psychiatric patients (5). The purpose of the current study by Tolner and colleagues is not only to revive attention for this neglected area of investigation but also to demonstrate the efficacy of 5% CO 2 , a clinically appropriate concentration, and to carry out a preliminary study of this intervention to treat acute seizures in the epilepsy monitoring unit.…”