Chemical Preconditioning with 3-Nitropropionic Acid in Gerbil Hippocampal Slices: Therapeutic Window and the Participation of Adenosine Receptor

Chemical Preconditioning with 3-Nitropropionic Acid in Gerbil Hippocampal Slices: Therapeutic Window and the Participation of Adenosine Receptor
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沙鼠海马切片中 3-硝基丙酸的化学预处理:治疗窗口和腺苷受体的参与

DOI:
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发表时间:
2000
影响因子:
5.3
通讯作者:
T. Sakaki
T. Sakaki
中科院分区:
医学2区
文献类型:
--
作者:
S. Aketa;H. Nakase;Y. Kamada;Ken;T. Sakaki

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亚毒性剂量的神经毒素3-硝基丙酸(3-NPA)诱导的缺血耐受最近被报道为“化学预处理”。"我们使用耐受现象的沙鼠海马切片模型,从电生理学角度研究了腺苷受体的治疗窗口和作用效果。3-在切片制备前3、24和72 h腹腔内给予4 mg/kg剂量的NPA。与对照组相比,缺氧3h和24h预处理组的缺氧去极化(HD)延迟时间延长(P <0.05),缺氧8min后的兴奋性突触后电位恢复明显改善(P <0.05)。HD延迟时间与恢复时间呈高度相关(r = 0.37,P <0.001)。这些作用完全逆转茶碱(20毫克/公斤),腺苷受体阻滞剂的管理。这些结果表明,3-NPA化学预处理诱导的早期发作(3小时)和持久(24小时)的耐受缺氧损伤兴奋性突触机制在海马通过延迟钙内流,腺苷受体的激活有助于这种神经保护作用。
Ischemic tolerance induced by a subtoxic dose of neurotoxin, 3-nitropropionic acid (3-NPA), was recently reported as "chemical preconditioning." We electrophysiologically investigated the therapeutic window and the effect via action at the adenosine receptor using a gerbil hippocampal slice model of the tolerance phenomenon. 3-NPA at the dose of 4 mg/kg was administered intraperitoneally at 3, 24, and 72 h prior to slice preparation. Prolonged delay to hypoxic depolarization (HD) and improvement of the field excitatory postsynaptic potential recovery following a fixed period of hypoxia (8 min) were observed in the groups pretreated at 3 and 24 h compared with the control (P < 0.05). Correlation between the delay to HD and the recovery was highly significant (r = 0.37, P < 0.001). These effects were completely reversed by administration of theophylline (20 mg/kg), an adenosine receptor blocker. These findings indicate that chemical preconditioning with 3-NPA induces early onset (3 h) and long-lasting (24 h) tolerance of hypoxic damage to excitatory synaptic mechanisms in the hippocampus by delayed calcium entry, and the activation of adenosine receptor contributes to this neuroprotective effect.
DOI: --
发表时间: 1990
期刊: Stroke
影响因子: 8.3
作者:
Somjen,GG;Aitken,PG;Balestrino,M;Herreras,O;Kawasaki,K
通讯作者: Kawasaki,K