STUDIES ON THE INTERRELATIONSHIP BETWEEN THE BLOOD-BRAIN BARRIER AND ENTRY OF VIRUSES INTO THE CENTRAL NERVOUS SYSTEM : I. THE EFFECT OF CARBON DIOXIDE ON TYPE II POLIOVIRUS INFECTION IN MICE

Inhalation of elevated concentrations of CO(2) produces a significant increase in the susceptibility of mice to intravenously inoculated Type II poliovirus. The CO(2) effect is directly proportional to the concentration; 2.5 minutes inhalation of a mixture of 30 per cent CO(2)-70 per cent O(2) produces maximal effects, while lower concentrations of CO(2) require correspondingly longer periods. The threshold level is 7 per cent; inhalation of lower concentrations, even for long periods of time, fails to enhance virus infectivity. Placing the animals in the CO(2) atmosphere before injection of virus does not influence susceptibility; virus must be in the circulation at the time CO(2) is inhaled if enhancement of infectivity is to be elicited. The effect is completely reversible, disappearing almost immediately upon withdrawal of the animals from the CO(2) atmosphere. CO(2) mediates an increase in the entry of virus into the CNS from the circulation but does not affect the spread of virus within the CNS; susceptibility of mice to intracerebrally inoculated poliovirus is not influenced by CO(2) inhalation. The mechanism(s) of action of CO(2) can be explained, in part, by the dilatation of cerebral blood vessels and increased rate of blood flow through the CNS produced by the CO(2). However, other factors, which remain unidentified, contribute to the net effect of CO(2). The relationship between the mechanism of action of CO(2) and the provoking effects of trauma and violent exercise in poliomyelitis is discussed. Also, a relationship between the CO(2) tension of the blood and environmental temperatures on poliovirus susceptibility is proposed.