Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist.
Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist.
复制标题
DOI：
10.1016/0014-2999(95)00498-x
复制
发表时间：
1995-12
影响因子：
5
通讯作者：
D. V. von Lubitz;R. Lin;K. Jacobson
中科院分区：
文献类型：
--
作者：
D. V. von Lubitz;R. Lin;K. Jacobson
尽管基于腺苷A1受体的疗法在治疗脑缺血和中风的潜力方面取得了重大进展，但对选择性刺激腺苷A2受体对脑血管骤停结果的影响知之甚少。鉴于腺苷A2受体在脑血流调节中的重要作用，我们观察了选择性腺苷受体激动剂2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5′-N-ethylcarboxoamidoadenosine和拮抗剂8-(3-氯苯乙烯)咖啡因对沙土鼠脑缺血10min结局的影响。APEC的急性治疗改善了缺血后血流的恢复和存活率，而不影响海马神经元的保存。CSC急性给药对脑血流量无明显影响，但对海马神经元有非常明显的保护作用。在缺血后最初的10天内，存活率显著提高。由于接受CSC急性治疗的动物随后死亡，这组动物的终点死亡率(缺血后14天)在统计学上与对照组没有差异。然而，急性CSC组的晚期死亡可能是由于脑缺血的全身性影响而不受该药物治疗的影响。APEC的慢性治疗导致所有研究指标在统计上都有显著改善。尽管慢性CSC治疗改善了缺血后的血流量，但其对神经元保存的影响微乎其微，在统计学上意义不大。死亡率仍未受到影响。结果提示，腺苷A2受体拮抗剂的急性治疗对全脑缺血的治疗价值有限。然而，由于应用CSC对脑缺血后血流的重建没有影响，因此用腺苷A2受体拮抗剂治疗中风可能是不可取的。需要进一步的研究来阐明长期服用作用于腺苷A2受体的药物是否对治疗中风和其他神经退行性疾病有用。
Despite significant progress in understanding of the potential of adenosine A1receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A2Areceptors on the outcome of a cerebrovascular arrest. In view of a major role played by adenosine A2receptors in the regulation of cerebral blood flow, we have investigated the effect of both acute and chronic administration of the selective adenosine receptor agonist 2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5′-N-ethylcarboxoamidoadenosine (APEC) and antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in gerbils. Acute treatment with APEC improved recovery of postischemic blood flow and survival without affecting neuronal preservation in the hippocampus. Acute treatment with CSC had no effect on the cerebral blood flow but resulted in a very significant protection of hippocampal neurons. Significant improvement of survival was present during the initial 10 days postischemia. Due to subsequent deaths of animals treated acutely with CSC, the end-point mortality (14 days postischemia) in this group did not differ statistically from that seen in the controls. It is, however, possible that the late mortality in the acute CSC group was caused by the systemic effects of brain ischemia that are not subject to the treatment with this drug. Chronic treatment with APEC resulted in a statistically significant improvement in all studied measures. Although chronic treatment with CSC improved postischemic blood flow, its effect on neuronal preservation was minimal and statistically insignificant. Mortality remained unaffected. The results indicate that the acute treatment with adenosine A2Areceptor antagonists may have a limited value in treatment of global ischemia. However, since administered CSC has no effect on the reestablishment of postischemic blood flow, treatment of stroke with adenosine A2Areceptor antagonists may not be advisable. Additional studies are necessary to elucidate whether chronically administered drugs acting at adenosine A2receptors may be useful in treatment of stroke and other neurodegenerative disorders.