Sulfonylurea receptor 1 in the germinal matrix of premature infants.
Sulfonylurea receptor 1 in the germinal matrix of premature infants.
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DOI：
10.1203/pdr.0b013e318186e5a9
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发表时间：
2008-12
影响因子：
3.6
通讯作者：
Gerzanich V
中科院分区：
文献类型：
--
作者：
Simard JM;Castellani RJ;Ivanova S;Koltz MT;Gerzanich V
脑性瘫痪（CP）的主要病因是脑性基质出血（GM）。GMH通常在缺氧/缺血事件之前发生，并且被认为是由GM中弱化的静脉破裂引起的。在CNS中，缺氧/缺血上调微血管内皮中磺酰脲受体1（SUR 1）调节的NCCa-ATP通道，ATP耗竭导致的通道激活是进行性继发性出血的原因。我们推测，这一通道可能是上调的GM早产儿的风险GMH。在这里，我们研究了表达的调节亚基的通道，SUR 1，其转录的前体，缺氧诱导因子1（HIF 1），在死后组织的早产儿，无论是在风险或谁持续GMH。我们发现区域特异性上调HIF 1和SUR 1蛋白和mRNA的GM组织相比，远程皮质组织。在大多数祖细胞中，SUR 1的上调是突出的，而在静脉中，SUR 1主要在持续GMH的婴儿中发现，与没有出血的婴儿相比。我们的数据表明，SUR 1-regulaterd NCCa-ATP通道可能与GMH，这些通道的药理学阻断可能会降低这种破坏性的早产儿并发症的发生率。
Germinal matrix (GM) hemorrhage (GMH) is a major cause of mortality and of life-long morbidity from cerebral palsy (CP). GMH is typically preceded by hypoxic/ischemic events and is believed to arise from rupture of weakened veins in the GM. In the CNS, hypoxia/ischemia upregulate sulfonylurea receptor 1 (SUR1) -regulated NCCa-ATP channels in microvascular endothelium, with channel activation by depletion of ATP being responsible for progressive secondary hemorrhage. We hypothesized that this channel might be upregulated in the GM of preterm infants at risk for GMH. Here, we studied expression of the regulatory subunit of the channel, SUR1, and its transcriptional antecedent, hypoxia inducible factor 1 (HIF1), in postmortem tissues of premature infants who either were at risk for or who sustained GMH. We found regionally specific upregulation of HIF1 and of SUR1 protein and mRNA in GM tissues, compared to remote cortical tissues. Upregulation was prominent in most progenitor cells, whereas in veins, SUR1 was found predominantly in infants who had sustained GMH compared to those without hemorrhage. Our data suggest that the SUR1-regulaterd NCCa-ATP channel may be associated with GMH, and that pharmacological block of these channels could potentially reduce the incidence of this devastating complication of prematurity.