The nature of increased blood‐cerebrospinal fluid barrier exchange during CO2 inhalation in newborn and adult rats

Abstract

Exposure of newborn (2-day-old) and adult rats to increasing levels of inspired carbon dioxide (5-15% CO2) resulted in increased steady-state cerebrospinal fluid/plasma ratios for a wide range of different-sized, lipid-insoluble permeability markers (molecular radius ranged from 0.43 nm for L-glucose to 5.3 nm for immunoglobulin G). In control animals breathing room air and animals exposed to an elevated level of inspired CO2, steady-state CSF/plasma ratios for all permeability markers were proportional to their free diffusion coefficient. Steady-state CSF/plasma ratios in newborn animals were significantly higher than in adult animals, and at all ages the ratios for animals exposed to CO2 were higher than the ratios in control animals. In contrast to the increased steady-state CSF/plasma ratios in animals exposed to elevated levels of inspired CO2, there was no significant difference in short-term (10 min after i.v. injection) CSF/plasma ratios for [14C]L-glucose between 10- to 20-day-old control rats and rats of similar age exposed to 10% inspired CO2. Steady-state experiments confirmed that CSF/plasma ratios for [14C]L-glucose in 20-day-old rats exposed to 10% inspired CO2 were raised significantly (twice those measured in control animals breathing room air). The lack of effect of raised CO2 on short-term CSF/plasma ratios indicates that the significant increases in steady-state CSF/plasma ratios, in animals exposed to elevated levels of inspired CO2, are not due to a general increase in the permeability of the blood-CSF or blood-brain barriers; they are likely to be accounted for by CO2-induced reductions in the rate of CSF secretion.