Neonatal cerebral hypoxia-ischemia: The effect of adenosine receptor antagonists
Neonatal cerebral hypoxia-ischemia: The effect of adenosine receptor antagonists
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DOI：
10.1016/s0028-3908(97)00139-1
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发表时间：
1997-09-01
影响因子：
4.7
通讯作者：
Hagberg, H
中科院分区：
文献类型：
--
作者：
Bona, E;Aden, U;Hagberg, H
研究了在新生儿缺氧缺血（HI）之前或之后给予非选择性（茶碱）、A（1）-（DPCPX）或A（2A）-选择性（SCH 58261）腺苷受体拮抗剂对7日龄大鼠14天后评价的脑损伤程度的影响。用原位杂交技术研究了茶碱（20 mg/kg）对即刻早期基因表达的可能影响。与对照组相比，HI前给予茶碱（20、30或60 mg/kg）分别使脑损伤减少48%（P < 0.001）、36%（P < 0.01）和34%（P < 0.05）。这种影响不能用温度、脑血流量、血气/酸碱状态或血糖在损伤期间的变化来解释。茶碱可增强c-fos和NFGI-A的表达。但不能阻止腺苷A（1）受体mRNA的减少。与对照组大鼠相比，SCH 58261（0.2或2 mg/kg）后处理分别使脑损伤降低了19%（P < 0.05）和14%（NS）。这与核心温度无关。DPCPX（2或10 mg/kg）对脑损伤的发展没有影响。总之，非选择性和A（2A）腺苷受体拮抗剂减少了未成熟动物HI模型中的脑损伤。(C)1997年爱思唯尔科学有限公司
The effects of nonselective (theophylline), A(1)-(DPCPX) or A(2A)-selective (SCH 58261) adenosine receptor antagonists administered before or after neonatal hypoxia-ischemia (HI) were studied on the extent of brain injury in 7-day-old rats evaluated after 14 days. A possible effect of theophylline (20 mg/kg) on expression of immediate early genes was studied with in situ hybridization. Theophylline (20, 30 or 60 mg/kg) given prior to HI reduced brain damage by 48% (P < 0.001), 36% (P < 0.01) and 34% (P < 0.05), respectively, compared to control rats. This effect was not explained by changes in temperature, cerebral blood flow, blood gas/acid base status or blood glucose during the insult. Theophylline enhanced the upregulation of c-fos and NFGI-A. during reperfusion but did not prevent the decrease in adenosine A(1) receptor mRNA. Posttreatment with SCH 58261 (0.2 or 2 mg/kg) reduced brain damage by 19% (P < 0.05) and 14% (NS), respectively, compared to control rats. which was unrelated to the core temperature. DPCPX (2 or 10 mg/kg) had no effect on the development of brain injury. In conclusion, nonselective and A(2A) adenosine receptor antagonists reduced brain injury in a model of HI in immature animals. (C) 1997 Elsevier Science Ltd.