Aims: 

The aim of the present study was to test the hypothesis that the neuroprotective effect of dexamethasone after global brain hypoxia-ischemia depends on its penetration extent into the brain, which is depended on the development of the brain-blood barrier, the age of animals.

Methods: 

Sprague-Dawley male rats were subjected to permanent bilateral common carotid artery occlusion.The effects of the intracerebroventricularly administered dexamethasone, the antiglucocorticoid mifepristone and their combination were measured on changes in water, Na⁺, K⁺ and Ca²⁺ contents of normal and hypoxic-ischemic brain. In a separate experiment the quantity of the intraperitoneally administered tritiated dexamethasone penetration was determined in the brain of several age-groups of rats. All the drugs were administered immediately after the introduction of hypoxia-ischemia.

Results: 

Intraperitoneally administered tritiated dexamethasone was able to penetrate into the brain of 1- or 2-week-old rats, but significantly less into the brain of 4-, 12- or 24-week-old animals. The considerable penetration of dexamethasone lasted about postnatal day 24, when the brain-blood barrier is fully developed. Intracerebroventricularly administered dexamethasone dose dependently inhibited the changes in water, Na⁺, K⁺ and Ca²⁺ contents of hypoxic-ischemic brain in adult rats. These inhibitions could be antagonized with mifepristone. The results suggest that the neuroprotective effect of dexamethasone is exercised through the glucocorticoid receptors in the brain.

Conclusion: 

The present findings support the hypothesis that the neuroprotective effect of dexamethasone on hypoxic-ischemic brain injury depends on its penetration extent into the brain, which is depended on the development of the brain blood barrier.