THE EFFECT OF LONG-TERM CAFFEINE TREATMENT ON HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE NEONATE

There is considerable concern over the widespread use of caffeine duri ng and after pregnancy. We have therefore examined the effect of perin atal caffeine use on the vulnerability of the immature brain to hypoxi c ischemia (HI). Rat pups were exposed to caffeine during the first 7 d after birth by addition of a low or a high dose (0.3 or 0.8 g/L) of caffeine to the drinking water of their dams. At 7 d the pups were exp osed to unilateral carotid occlusion + exposure to 7.70% oxygen for 10 0 min. The extent of HI brain damage was evaluated 2 wk after the insu lt. The effects of caffeine on A(1) and A(2a) receptors, A(1) mRNA and A(2a) mRNA, were examined by receptor autoradiography and in situ hyb ridization. Caffeine, theobromine, theophylline, and paraxanthine were analyzed in plasma of separate animals. Exposure to caffeine reduced HI brain damage from 40.3 +/- 3.2% in controls to 29.8 +/- 4.0% (p < 0 .05) in low dose and 33.7 +/- 3.9% (NS) in the high dose group. The A( 1) receptor density measured as [H-3]-1,3-dipropyl-8-cyclopentyl xanth ine ([H-3]-DPCPX) binding was not significantly affected after low dos e caffeine but increased in the brain of rat pups in the high dose gro up. The A(2a) receptor density measured as yl)-phenethylamino]-5'-N-et hylcarboxamidoadenosine ([H-3]-CGS 21680) binding and the expression o f A(1) mRNA and A(2a) mRNA were not altered by caffeine treatment. In conclusion, low dose caffeine exposure (plasma levels corresponding to umbilical cord plasma in newborns of coffee-consuming mothers) reduce d HI brain damage by 30% in 7-d-old rats. This ameliorating effect cou ld not be accounted for by up-regulation of adenosine receptors.