Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region
Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region
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DOI：
10.1007/s11064-005-8510-z
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发表时间：
2005-11-01
影响因子：
4.4
通讯作者：
Burda, R
中科院分区：
文献类型：
--
作者：
Burda, J;Matiasová, M;Burda, R
在缺血耐受实验中，在缺血30分钟前2天进行5分钟缺血时，CA1神经元的存活率达到了95.8%。然而，在不进行致死性缺血的情况下，我们发现CA1中有45.8%的神经元变性。这意味着40%的CA1神经元从缺血后变性中恢复是由第二次病理生理应激引起的。这些发现鼓励我们假设在致死性缺血后48小时进行第二次病理生理应激可以有效地预防延迟性神经元死亡。我们的研究结果表明，尽管8分钟的致死性缺血破坏了49.9%的CAI神经元，10分钟的缺血破坏了71.6%的CA1神经元，但三种不同的第二次病理生理应激技术能够保护CA1损伤和空间学习/记忆功能障碍。去甲肾上腺素（3.1 μ mol/kg i.p）在缺血8 min后2天给药，可保护94.2%，缺血10 min后2天给药，可保护89.9%，缺血10 min后2天给药，可保护77.5%的CA1神经元。因此，如果在致死性缺血后的适当时间施加第二次病理生理应激，则为挽救海马CA1区域的神经元以对抗延迟性神经元死亡提供了一个重要的治疗窗口。
In ischemic tolerance experiment, when we applied 5-min ischemia 2 days before 30-min ischemia, we achieved a remarkable (95.8%) survival of CA1 neurons. However, when we applied 5-min ischemia itself, without following lethal ischemia, we found out 45.8% degeneration of neurons in the CA1. This means that salvage of 40% CA1 neurons from postischemic degeneration was initiated by the second pathophysiological stress. These findings encouraged us to hypothesize that the second pathophysiological stress used 48 h after lethal ischemia can be efficient in prevention of delayed neuronal death. Our results demonstrate that whereas 8 min of lethal ischemia destroys 49.9% of CAI neurons, 10 min of ischemia destroys 71.6% of CA1 neurons, three different techniques of the second pathophysiological stress are able to protect against both: CA1 damage as well as spatial learning/memory dysfunction. Bolus of norepinephrine (3.1 mu mol/kg i.p.) used two days after 8 min ischemia saved 94.2%, 6 min ischemia applied 2 days after 10 min ischemia rescued 89.9%, and an injection of 3-nitropropionic acid (20 mg/kg i.p.) applied two days after 10 min ischemia protected 77.5% of CA1 neurons. Thus, the second pathophysiological stress, if applied at a suitable time after lethal ischemia, represents a significant therapeutic window to opportunity for salvaging neurons in the hippocampal CA1 region against delayed neuronal death.