STUDIES ON THE INTERRELATIONSHIP BETWEEN THE BLOOD-BRAIN BARRIER AND ENTRY OF VIRUSES INTO THE CENTRAL NERVOUS SYSTEM

Abstract

Inhalation of elevated concentrations of CO2 produces a significant increase in the susceptibility of mice to intravenously inoculated Type II poliovirus. The CO2 effect is directly proportional to the concentration; 2.5 minutes inhalation of a mixture of 30 per cent CO2-70 per cent O2 produces maximal effects, while lower concentrations of CO2 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 CO2 atmosphere before injection of virus does not influence susceptibility; virus must be in the circulation at the time CO2 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 CO2 atmosphere. CO2 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 CO2 inhalation. The mechanism(s) of action of CO2 can be explained, in part, by the dilatation of cerebral blood vessels and increased rate of blood flow through the CNS produced by the CO2. However, other factors, which remain unidentified, contribute to the net effect of CO2. The relationship between the mechanism of action of CO2 and the provoking effects of trauma and violent exercise in poliomyelitis is discussed. Also, a relationship between the CO2 tension of the blood and environmental temperatures on poliovirus susceptibility is proposed.