Battle of the hemichannels - Connexins and Pannexins in ischemic brain injury
Battle of the hemichannels - Connexins and Pannexins in ischemic brain injury
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DOI：
10.1016/j.ijdevneu.2014.12.007
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发表时间：
2015-10-01
影响因子：
1.8
通讯作者：
Gunn, A. J.
中科院分区：
文献类型：
--
作者：
Davidson, J. O.;Green, C. R.;Gunn, A. J.
早产儿或足月新生儿的全身缺血性损伤或局灶性缺血性中风可能导致围产期缺血性脑损伤。 HI 损伤最显着的特征之一是，在细胞氧化代谢初步恢复后，会出现延迟的“继发性”线粒体衰竭，随着时间的推移，线粒体衰竭会从受损最严重的区域向外扩散到之前未受损的区域。这种继发性衰竭伴随着短暂的癫痫发作和细胞毒性水肿。这种传播的具体机制尚不清楚，但它至少部分与抑郁症的传播有关，抑郁症可以触发邻近未受伤组织的细胞死亡。 Connexin 和 Pannexin 半通道均可介导旁分泌分子的释放，而旁分泌分子又通过释放细胞内介质（例如 ATP、NAD(+) 或谷氨酸）或通过异常延长的开放以允许细胞水肿来传播细胞死亡信息。本综述将讨论围绕连接蛋白和潘连接蛋白半通道的相对贡献以及它们可能导致缺血性脑损伤扩散的机制的争议。 (C) 2014 Elsevier Ltd. 保留所有权利。
Perinatal ischemic brain injury can occur as a result of a global ischemic insult or focal ischemic stroke in the preterm or full-term neonate. One of the most striking features of HI injury is that, after initial recovery of cellular oxidative metabolism, there is a delayed, 'secondary' mitochondrial failure that spreads over time from the most severely damaged areas outwards, into previously undamaged regions. This secondary failure is accompanied by transient seizure activity and cytotoxic edema.The specific mechanisms of this spread are poorly understood, but it is at least partly associated with spreading waves of depression that can trigger cell death in neighboring uninjured tissues. Both Connexin and Pannexin hemichannels may mediate release of paracrine molecules that in turn propagate cell death messages by releasing intracellular mediators, such as ATP, NAD(+), or glutamate or by abnormally prolonged opening to allow cell edema. This review will discuss the controversy around the relative contribution of both Connexin and Pannexin hemichannels and mechanisms by which they may contribute to the spread of ischemic brain injury. (C) 2014 Elsevier Ltd. All rights reserved.