Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain
Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain
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DOI：
10.1007/s10571-006-9036-x
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发表时间：
2006-11-01
影响因子：
4
通讯作者：
Burda, Rastislav
中科院分区：
文献类型：
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作者：
Burda, Jozef;Danielisova, Viera;Burda, Rastislav
1. 本研究的目的是验证致死性缺血后 2 天使用的后处理对于保护选择性脆弱脑神经元免受延迟性神经元死亡的作用。2．大鼠短暂前脑缺血8分钟、10分钟或15分钟（四血管闭塞模型）用作初始致死性缺血。 Fluoro Jade B（神经变性标记物）和 NeuN（一种特定的神经元标记物）用于可视化缺血后 7 或 28 天的变化，无论是否经过延迟后处理。 3．我们的结果证实，如果在正确的时间和最佳的强度下进行后处理，可以防止延迟性神经元死亡的过程。至少三种称为预处理的技术可用作后处理：短时缺血、3-硝基丙酸和去甲肾上腺素。预防选择性脆弱神经元死亡的主要作用包括后处理后前 5 小时内蛋白质的合成。仅缺血 10 分钟即可导致海马 70% 的锥体 CA1 神经元死亡。如果与后处理同时注射蛋白质合成抑制剂（放线菌酮），则会抑制后处理的有益效果，并导致 50% 的 CA1 神经元发生神经变性。然而，当后处理5小时后注射Cycloheximide时，这种治疗导致90%的CA1神经元存活。4．尽管后处理可在缺血 10 分钟内显着保护海马 CA1 神经元，但在缺血 15 分钟时其功效已耗尽。然而，在经历 15 分钟缺血等破坏性损伤后，后处理对不太敏感的神经元群体（皮层和纹状体）的保护作用非常好。该声明还意味着，长达 15 分钟的缺血后处理不会导致第一次和第二次应力产生的损伤累积。
1. The aim of this study was to validate the role of postconditioning, used 2 days after lethal ischemia, for protection of selectively vulnerable brain neurons against delayed neuronal death.2. Eight, 10, or 15 min of transient forebrain ischemia in rat (four-vessel occlusion model) was used as initial lethal ischemia. Fluoro Jade B, the marker of neurodegeneration, and NeuN, a specific neuronal marker were used for visualization of changes 7 or 28 days after ischemia without and with delayed postconditioning.3. Our results confirm that postconditioning if used at right time and with optimal intensity can prevent process of delayed neuronal death. At least three techniques, known as preconditioners, can be used as postconditioning: short ischemia, 3-nitropropionic acid and norepinephrine. A cardinal role for the prevention of death in selectively vulnerable neurons comprises synthesis of proteins during the first 5 h after postconditioning. Ten minutes of ischemia alone is lethal for 70% of pyramidal CA1 neurons in hippocampus. Injection of inhibitor of protein synthesis (Cycloheximide), if administered simultaneously with postconditioning, suppressed beneficial effect of postconditioning and resulted in 50% of CA1 neurons succumbing to neurodegeneration. Although, when Cycloheximide was injected 5 h after postconditioning, this treatment resulted in survival of 90% of CA1 neurons.4. Though postconditioning significantly protects hippocampal CA1 neurons up to 10 min of ischemia, its efficacy at 15 min ischemia is exhausted. However, protective impact of postconditioning in less-sensitive neuronal populations (cortex and striatum) is very good after such a damaging insult like 15 min ischemia. This statement also means that up to 15 min of ischemia, postconditioning does not induce cumulation of injuries produced by the first and the second stress.