THE EFFECT OF LONG-TERM CAFFEINE TREATMENT ON HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE NEONATE
THE EFFECT OF LONG-TERM CAFFEINE TREATMENT ON HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE NEONATE
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DOI：
10.1203/00006450-199509000-00007
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发表时间：
1995-09-01
影响因子：
3.6
通讯作者：
HAGBERG, H
中科院分区：
文献类型：
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作者：
BONA, E;ADEN, U;HAGBERG, H
人们对怀孕期间和怀孕后广泛使用咖啡因有相当大的担忧。因此，我们研究了围产期使用咖啡因对未成熟大脑对缺氧缺血(HI)易感性的影响。在仔鼠出生后7d内，在其水坝的饮用水中加入低剂量或高剂量(0.3g/L或0.8g/100g)咖啡因。7d后，将幼鼠暴露于一侧颈总动脉结扎+7.70%氧气暴露100min。伤后2wk评定HI脑损伤程度。用受体放射自显影和原位杂交法检测咖啡因对A(1)和A(2a)受体A(1)和A(2a)mRNA的影响。分析了不同动物血浆中的咖啡因、可可碱、茶碱和对黄嘌呤。暴露于咖啡因可将HI脑损伤从对照组的40.3+/-3.2%降低到29.8+/-4.0%(p<；0.05)和33.7+/-3.9%(NS)。低剂量咖啡因对[H-3]-1，3-二丙基-8-环戊基黄嘌呤([H-3]-DPCPX)结合的A(1)受体密度无明显影响，但高剂量组大鼠脑内A(1)受体密度增加。咖啡因处理不改变A(2a)受体密度和A(1)、A(2a)[H-3]-2[p-(2-carbonylethyl)-phenethylamino]-5‘-N-ethylcarboxamidoadenosine([H-3]-CG 21680)结合。总而言之，低剂量咖啡因暴露(相当于饮用咖啡的母亲的新生儿脐带血浆的血浆水平)将7日龄大鼠的HI脑损伤减少了30%。这种改善作用不能通过上调腺苷受体来解释。
There is considerable concern over the widespread use of caffeine during and after pregnancy. We have therefore examined the effect of perinatal caffeine use on the vulnerability of the immature brain to hypoxic 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 exposed to unilateral carotid occlusion + exposure to 7.70% oxygen for 100 min. The extent of HI brain damage was evaluated 2 wk after the insult. 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 hybridization. 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 xanthine ([H-3]-DPCPX) binding was not significantly affected after low dose caffeine but increased in the brain of rat pups in the high dose group. The A(2a) receptor density measured as [H-3]-2[p-(2-carbonylethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine ([H-3]-CGS 21680) binding and the expression of 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) reduced HI brain damage by 30% in 7-d-old rats. This ameliorating effect could not be accounted for by up-regulation of adenosine receptors.