Cerebral pO₂, pCO₂ and pH: Changes During Convulsive Activity and their Significance for Spontaneous Arrest of Seizures

Abstract

SUMMARY The present study on rats and cats aimed to clarify the role played by hypoxia, hypercapnia and acidosis in spontaneous arrest of seizures. In most experiments cortical pO2 declined during seizure activity, whereas pCO2 increased. Occasionally, however, reverse reactions occurred. Since the increase in cortical blood flow varied over a wide range, it could account for the fact that gas tension did not always change in the same direction or to the same degree during a seizure. Cessation of seizure activity was independent of the degree and direction of the changes in gas tension. When seizures were arrested by experimentally produced hypoxia, cortical and spinal neurons always showed a distinct depolarization. When convulsive discharges were suppressed by artificial increase in PCO2 most units were concomitantly hyperpolarized. When seizures ceased spontaneously, both cortical and spinal neurons showed a steep re‐ and hyperpolarization, independent of concomitant fluctuations in local gas tension. The findings lead to the conclusion that the degree of hypoxia and hypercapnia usually encountered during prolonged seizure activity does not reach the critical level sufficient to depress seizure activity. It must be assumed that spontaneous seizure termination is based, primarily, on neuronal processes. RESUME Cette étude se propose de préciser, chez les rats et les chats, le rôle de l'hypoxie, de l'hypercapnie et de l'acidose dans l'arrêt des crises spontanées. Dans la majorité des expériences, Ia pO2 au niveau cortical diminue pendant la crise, tandis que la pCO2 augmente, quoique occasionnellement, on ait observé le contraire. La très grande variabilité de l'augmentation de la circulation sanguine cérébrale pouvait rendre compte du fait que pendant une crise, la tension des gaz ne changeait pas toujours dans le même sens ou dans les mêmes limites. L'arrêt de la crise était indépendant du degré et du type des modifications de la tension des gaz. Lorsque les crises étaient arrêtées à la suite d'une anoxie provoquée expérimentalement, on a toujours observé une dépolarisation des neurones corticaux spinaux. Lorsque les décharges convulsives étaient supprimées par une augmentation artificielle de la pCO2, la majorité des neurones était parallèlement hyperpolarisée. Lorsque les crises s'arrêtaient spontanément, les neurones du cortex et de la moelle montraient une rapide repolarisation et ensuite une hyperpolarisation indépendamment des fluctuations concomitantes de la tension des gaz. Ces données amènent à la conclusion que le degré d'hypoxie et d'hypercapnie qu'on observe habituellement pendant des crises prolongées n'atteint pas un niveau suffisant pour déprimer l'activité paroxystique. On doit en tirer la conclusion que l'arrêt spontané d'une crise est dûà des processus nerveux.

Importance of Vascular Responses in Determining Cortical Oxygenation during Recurrent Paroxysmal Events of Varying Duration and Frequency of Repetition

“…Apparently, the coupling between cerebral oxidative metabolism and blood flow is such that a recovery period is required for a full return to responsiveness following each burst of parox ysmal activity. This idea is supported by reports describing progressive decreases in cerebrovas cular reactivity (Kontos et aI., 1978;Blennow et aI., 1979), cerebrovascular resistance (Magnaes and Nomes, 1974), and the magnitude of phasic increases in CBF (Shalit, 1965;Caspers and Speckman, 1972) during recurrent seizures. These cerebrovascular changes already have been impli cated in the transition of cerebral P02 responses from increases to decreases and cytochrome a,a3 responses from oxidations to reductions (Caspers and Speckman, 1972;Kreisman et al, 1981bKreisman et al, , 1983a.…”

“…This idea is supported by reports describing progressive decreases in cerebrovas cular reactivity (Kontos et aI., 1978;Blennow et aI., 1979), cerebrovascular resistance (Magnaes and Nomes, 1974), and the magnitude of phasic increases in CBF (Shalit, 1965;Caspers and Speckman, 1972) during recurrent seizures. These cerebrovascular changes already have been impli cated in the transition of cerebral P02 responses from increases to decreases and cytochrome a,a3 responses from oxidations to reductions (Caspers and Speckman, 1972;Kreisman et al, 1981bKreisman et al, , 1983a. Collectively, these data suggest that transition from oxygen sufficiency to insufficiency during recurrent seizures is caused by uncoupling of appropriate ce rebrovascular responses from neuronal and meta bolic activity.…”

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

“…The exact mechanisms by which tissue pH and neuronal density may influence each other are not known yet. Changes in the physiological parameters of neurons and glial cells, and alterations in glutamate uptake and calcium metabolism, have been associated with changes in the intracellular or extracellular tissue pH (Balestrino and Somjen, 1988;Caspers and Speckmann, 1972;Dipolo and Beauge, 1982;Goldman et al, 1989;Gruol et al, 1980;Pappas et al, 1994;Robello et al, 1994;Takahashi et al, 1995). It is also known that changes in tissue pH are associated with certain pathological conditions such as ischemia or head injury (Billups and Attwell, 1996;Cadoux-Hudson et al, 1990;Smith et al, 1986).…”

Mechanisms of Regulation of Cerebral Microflow during Bicuculline-Induced Seizures in Anaesthetized Cats

“…Ingvar et al (1962) and Meyer et al (1966) reported that seizure activity of the cerebral cortex was accom panied by a decrease in local tissue Po 2 • From their measurements of the diameter of pial arteries before and after administration of metrazol, Wei et al (1977) deduced that during seizures dilation was mediated, at least in part, by activation of a meta bolic mechanism dependent on the production of tissue hypoxia. Caspers and Speckmann (1972) found a reduction of tissue P0 2 predominating during the seizure attacks. However, the rate of repetition of convulsions was important regarding the role of tissue Po 2 • During the first convulsions in a series, tissue P0 2 tended to rise rather than to fall.…”