Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus:: role of adenosine receptors
Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus:: role of adenosine receptors
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DOI：
10.1038/sj.bjp.0705442
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发表时间：
2003-09-01
影响因子：
7.3
通讯作者：
Pedata, F
中科院分区：
文献类型：
--
作者：
Pugliese, AM;Latini, S;Pedata, F
1脑缺血预处理包括降低神经元组织对进一步、更严重的缺血性损伤的敏感性。我们在细胞外记录海马脑片的场epsps（fepsps），以建立体外缺血预适应模型，并评估A（1），A（2A）和A（3）腺苷受体在这种现象中的作用。2缺血损伤的应用，通过葡萄糖和氧剥夺7分钟获得，产生了不可逆的突触传递抑制。缺血预处理诱导的四个缺血损伤（2分钟），由13分钟的常氧条件下分离。30分钟后，施加7分钟的缺血性损伤。该方案基本上保护了组织免受突触活性的不可逆抑制。3选择性腺苷A（1）受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX，100 nM）完全阻止了预处理的保护作用。与对照切片相比，选择性腺苷A（2A）受体拮抗剂4-（2-[7-氨基-2-（2-呋喃基）[1，2，4]三唑并[2，3-a][1，3，5]三嗪-5-基氨基]乙基）苯酚（ZM 241385，100 nM）未改变fepsp恢复的幅度。选择性A（3）腺苷受体拮抗剂3-丙基-6-乙基-5-[乙基（硫代）羰基]-2-苯基-4-丙基-3-吡啶羧酸酯（MRS 1523，100 nM）显著改善缺血7分钟后fepsps的恢复。4我们的研究结果表明，体外缺血预处理使CA 1海马神经元对长时间暴露于缺血具有抵抗力。腺苷通过刺激A（1）受体在引发预适应的细胞机制中起关键作用; A（2A）受体不参与此现象，而A（3）受体激活对缺血预适应有害。
1 Ischemic preconditioning in the brain consists of reducing the sensitivity of neuronal tissue to further, more severe, ischemic insults. We recorded field epsps (fepsps) extracellularly from hippocampal slices to develop a model of in vitro ischemic preconditioning and to evaluate the role of A(1), A(2A) and A(3) adenosine receptors in this phenomenon.2 The application of an ischemic insult, obtained by glucose and oxygen deprivation for 7 min, produced an irreversible depression of synaptic transmission. Ischemic preconditioning was induced by four ischemic insults (2 min each) separated by 13 min of normoxic conditions. After 30 min, an ischemic insult of 7 min was applied. This protocol substantially protected the tissue from the irreversible depression of synaptic activity.3 The selective adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), completely prevented the protective effect of preconditioning. The selective adenosine A(2A) receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4] triazolo[2,3-a][1,3,5] triazin-5-ylamino] ethyl) phenol (ZM 241385, 100 nM) did not modify the magnitude of fepsp recovery compared to control slices. The selective A(3) adenosine receptor antagonists, 3-propyl-6-ethyl-5[ethyl(thio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523, 100 nM) significantly improved the recovery of fepsps after 7 min of ischemia.4 Our results show that in vitro ischemic preconditioning allows CA1 hippocampal neurons to become resistant to prolonged exposure to ischemia. Adenosine, by stimulating A(1) receptors, plays a crucial role in eliciting the cell mechanisms underlying preconditioning; A(2A) receptors are not involved in this phenomenon, whereas A(3) receptor activation is harmful to ischemic preconditioning.