Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, New York, USA.
J Neurosci Res. 2010 May 1;88(6):1193-204. doi: 10.1002/jnr.22301.
Germinal matrix (GM) vasculature is selectively vulnerable to hemorrhage in premature infants during the first 48 hr of life. This is attributed to rapid angiogenesis of this brain region, resulting in formation of nascent vessels that show a paucity of pericytes and immaturity of extracellular matrix. Integrins are key regulators of angiogenesis and contribute to stabilization of cerebral vasculature by providing endothelial- and astrocyte-matrix adhesion. Therefore, we asked whether GM exhibited a distinct regional pattern of integrin expression that was dissimilar from that of the cerebral cortex and white matter in human fetuses and premature infants. To this end, we measured protein and gene expression of integrins in the GM, cortex, and white matter of human fetuses (15-22 weeks), premature infants (23-35 weeks), and mature infants (36-40 weeks). We found that protein levels of alpha5beta1 integrin were greater in the GM than in the cortex or white matter by 1.6-fold for both fetuses and premature infants. alpha5beta1 integrin mRNA expression was higher in the GM than in the cortex or white matter by 2-fold for fetuses but not for premature infants. alphaVbeta3, alphaVbeta5, alphaVbeta8, and alpha4beta1 integrin expression were comparable among GM, cortex, and white matter in fetuses and premature infants. Because alpha5beta1 integrin is a central regulator of angiogenesis, its elevation in the GM of fetuses and premature infants indicates that this might be a key activator of endothelial proliferation in this brain region. We speculate that selective alpha5beta1 integrin inhibition might suppress angiogenesis in the GM and thus prevent brain hemorrhage in premature infants.
生发基质（GM）血管在早产儿生命的头 48 小时内特别容易发生出血。这归因于该脑区的快速血管生成，导致新生血管形成，周细胞稀少，细胞外基质不成熟。整合素是血管生成的关键调节剂，通过提供内皮细胞和星形胶质细胞-基质黏附，有助于稳定脑血管。因此，我们想知道 GM 是否表现出与胎儿和早产儿大脑皮层和白质不同的整合素表达的独特区域模式。为此，我们测量了 GM、皮层和白质中整合素的蛋白和基因表达，包括胎儿（15-22 周）、早产儿（23-35 周）和足月儿（36-40 周）。我们发现，GM 中 alpha5beta1 整合素的蛋白水平比皮层或白质高 1.6 倍，无论是在胎儿还是早产儿中。GM 中 alpha5beta1 整合素的 mRNA 表达比皮层或白质高 2 倍，而在早产儿中则没有。在胎儿和早产儿中，GM、皮层和白质中 alphaVbeta3、alphaVbeta5、alphaVbeta8 和 alpha4beta1 整合素的表达相当。由于 alpha5beta1 整合素是血管生成的核心调节剂，其在胎儿和早产儿 GM 中的升高表明这可能是该脑区内皮细胞增殖的关键激活剂。我们推测，选择性 alpha5beta1 整合素抑制可能抑制 GM 中的血管生成，从而防止早产儿脑出血。
