Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia
Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia
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DOI：
10.1161/01.str.0000182239.75969.d8
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发表时间：
2005-10-01
期刊：
影响因子：
8.3
通讯作者：
Rozental, R
中科院分区：
文献类型：
--
作者：
de Pina-Benabou, MH;Szostak, V;Rozental, R
背景和目的-我们研究了间隙连接在氧-葡萄糖剥夺（OGD）引起的脑损伤和迟发性神经元死亡中的作用。以及在OGD后切片培养物中和在宫内缺氧缺血（HI）后发育大鼠中的电生理和荧光细胞死亡测定。在切片培养中，OGD持续增加缝隙连接偶联，并强烈激活凋亡标记物caspase-3。差距连接阻断剂甘珀酸应用于海马切片培养前，期间，或60分钟后OGD显着减少迟发性神经元死亡。宫内HI后立即给予甘珀酸缺血幼崽，防止caspase-3激活，并显着减少长期neuronal damage.Conclusions -缝隙连接阻断可能是一种有用的治疗工具，以尽量减少围产期和出生后早期HI产生的脑损伤。
Background and Purpose - We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD).Methods - Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI).Results - OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage.Conclusions - Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.