Zinc and excitotoxic brain injury: A new model
Zinc and excitotoxic brain injury: A new model
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DOI：
10.1177/1073858403255840
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发表时间：
2004-02-01
期刊：
影响因子：
5.6
通讯作者：
Cuajungco, MP
中科院分区：
文献类型：
--
作者：
Frederickson, CJ;Maret, W;Cuajungco, MP
自从提出突触释放的Zn 2+可能有助于癫痫发作、中风和脑创伤后的兴奋性毒性脑损伤以来，已经有近15年的时间了。在最初的“锌易位”模型中，提出突触释放的Zn 2+离子穿透突触后神经元，引起损伤。根据该模型，在裂隙中螯合锌被预测为具有神经保护作用。这被证明是正确的：锌螯合剂已被证明是非常有效的，在许多范例中减少兴奋毒性神经元损伤。有前途的新的锌基治疗中风，头部创伤，癫痫性脑损伤正在开发中。然而，新的证据表明，最初的易位模型是不完整的。多达三种来源的有毒锌离子可能有助于兴奋毒性：突触前囊泡，突触后锌螯合蛋白，和（更推测）线粒体池。作者提出了一种新的锌电流和锌毒性模型，为锌选择性螯合治疗干预提供了更多的机会。
It has been nearly 15 years since the suggestion that synaptically released Zn2+ might contribute to excitotoxic brain injury after seizures, stroke, and brain trauma. In the original "zinc-translocation" model, it was proposed that synaptically released Zn2+ ions penetrated postsynaptic neurons, causing injury. According to the model, chelating zinc in the cleft was predicted to be neuroprotective. This proved to be true: zinc chelators have proved to be remarkably potent at reducing excitotoxic neuronal injury in many paradigms. Promising new zinc-based therapies for stroke, head trauma, and epileptic brain injury are under development. However, new evidence suggests that the original translocation model was incomplete. As many as three sources of toxic zinc ions may contribute to excitotoxicity: presynaptic vesicles, postsynaptic zinc-sequestering proteins, and (more speculatively) mitochondrial pools. The authors present a new model of zinc currents and zinc toxicity that offers expanded opportunities for zinc-selective therapeutic chelation interventions.