Ment L R, Stewart W B, Ardito T A, Madri J A
Department of Pediatrics, Yale University School of Medicine, New Haven, Conn. 06510.
Stroke. 1991 Mar;22(3):390-5. doi: 10.1161/01.str.22.3.390.
Intraventricular hemorrhage, or hemorrhage into the germinal matrix tissues of the developing brain, remains a common problem of preterm infants. The "risk period" for this insult is the first 3-4 postnatal days. We hypothesized that this risk period for hemorrhage is related to rapid perinatal maturation of the germinal matrix vasculature and employed the newborn beagle pup model for the study of this maturation. Newborn beagle pups (n = 30) were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density between postnatal days 1 and 4. Germinal matrix sections were also stained for antibodies to alpha-smooth muscle actin, collagen IV, collagen V, desmin, factor VIII-related antigen, fibronectin, glial fibrillary acidic protein, laminin, transferrin, and vimentin. Vasculature staining by alpha-smooth muscle actin was not noted until postnatal day 10, and differential staining was detected for antibodies to laminin and collagen V. Quantification of staining intensity by confocal microscopy demonstrated a significant increase in both extracellular matrix components at postnatal day 4 compared with day 1 (p less than 0.05 for both). These basement membrane proteins may add sufficient structural integrity to germinal matrix vessels to prevent capillary rupture and thus intraventricular hemorrhage.
脑室内出血,即出血进入发育中大脑的生发基质组织,仍然是早产儿的常见问题。这种损伤的“风险期”是出生后的头3 - 4天。我们假设这种出血风险期与生发基质血管系统的围产期快速成熟有关,并采用新生比格犬幼崽模型来研究这种成熟过程。将30只新生比格犬幼崽麻醉后用缓冲福尔马林进行全身灌注;取出大脑并准备进行免疫组织化学研究。用刀豆凝集素染色的切片显示,出生后第1天和第4天生发基质血管密度没有差异。生发基质切片还用抗α - 平滑肌肌动蛋白、IV型胶原、V型胶原、结蛋白、VIII因子相关抗原、纤连蛋白、胶质纤维酸性蛋白、层粘连蛋白、转铁蛋白和波形蛋白的抗体进行染色。直到出生后第10天才观察到α - 平滑肌肌动蛋白对血管系统的染色,并且检测到层粘连蛋白和V型胶原抗体的差异染色。通过共聚焦显微镜对染色强度进行定量分析表明,与第1天相比,出生后第4天细胞外基质成分均显著增加(两者p均小于0.05)。这些基底膜蛋白可能为生发基质血管增加足够的结构完整性,以防止毛细血管破裂,从而预防脑室内出血。