Department of Physiology, The University of Auckland, Auckland, New Zealand.
The Ritchie Centre, Hudson Institute of Medical Research, Victoria, Australia.
Sci Rep. 2017 Jul 24;7(1):6304. doi: 10.1038/s41598-017-06683-1.
Basal ganglia injury at term remains a major cause of disability, such as cerebral palsy. In this study we tested the hypotheses that blockade of astrocytic connexin hemichannels with a mimetic peptide would improve survival of striatal phenotypic neurons after global cerebral ischaemia in term-equivalent fetal sheep, and that neuronal survival would be associated with electrophysiological recovery. Fetal sheep (0.85 gestation) were randomly assigned to receive a short or long (1 or 25 h) intracerebroventricular infusion of a mimetic peptide or vehicle, starting 90 minutes after 30 minutes of cerebral ischaemia. Sheep were killed 7 days after ischaemia. Cerebral ischaemia was associated with reduced numbers of calbindin-28k, calretinin, parvalbumin and GAD positive striatal neurons (P < 0.05 ischaemia + vehicle, n = 6 vs. sham ischaemia, n = 6) but not ChAT or nNOS positive neurons. Short infusion of peptide (n = 6) did not significantly improve survival of any striatal phenotype. Long infusion of peptide (n = 6) was associated with increased survival of calbindin-28k, calretinin, parvalbumin and GAD positive neurons (P < 0.05 vs. ischaemia + vehicle). Neurophysiological recovery was associated with improved survival of calbindin-28k, calretinin and parvalbumin positive striatal neurons (P < 0.05 for all). In conclusion, connexin hemichannel blockade after cerebral ischaemia in term-equivalent fetal sheep improves survival of striatal GABA-ergic neurons.
基底节损伤仍是导致残疾的主要原因，例如脑瘫。在这项研究中，我们检验了以下假设：用模拟肽阻断星形胶质细胞缝隙连接半通道，会改善足月胎羊全脑缺血后纹状体表型神经元的存活，并且神经元存活与电生理恢复有关。将胎羊（0.85 孕期）随机分为接受短或长（1 或 25 小时）脑室内模拟肽或载体输注组，从 30 分钟脑缺血后 90 分钟开始。在缺血后 7 天处死羊。脑缺血与 calbindin-28k、calretinin、parvalbumin 和 GAD 阳性纹状体神经元数量减少有关（P<0.05 缺血+载体，n=6 与假缺血，n=6），但与 ChAT 或 nNOS 阳性神经元无关。短时间输注肽（n=6）并未显著改善任何纹状体表型的存活。长时间输注肽（n=6）与 calbindin-28k、calretinin、parvalbumin 和 GAD 阳性神经元的存活增加有关（P<0.05 与缺血+载体）。神经生理恢复与 calbindin-28k、calretinin 和 parvalbumin 阳性纹状体神经元存活的改善有关（P<0.05 所有）。总之，足月胎羊全脑缺血后缝隙连接半通道阻断可改善纹状体 GABA 能神经元的存活。
