Ellison J A, Velier J J, Spera P, Jonak Z L, Wang X, Barone F C, Feuerstein G Z
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Stroke. 1998 Aug;29(8):1698-706; discussion 1707. doi: 10.1161/01.str.29.8.1698.
Microglia and astrocytes in the peri-infarct region are activated in response to focal stroke. A critical function of activated glia is formation of a protective barrier that ultimately forms a new glial-limiting membrane. Osteopontin, a provisional matrix protein expressed during wound healing, is induced after focal stroke. The present study was performed to determine the spatial and temporal expression of osteopontin and its integrin receptor alpha(v)beta3 during formation of the peri-infarct gliotic barrier and subsequent formation of a new glial-limiting membrane.
Spontaneously hypertensive rats (n = 19) were subjected to permanent occlusion of the middle cerebral artery and killed 3, 6, and 24 hours and 2, 5, and 15 days after occlusion. The spatial and temporal expression of osteopontin mRNA was determined by in situ hybridization, and that of osteopontin ligand and its integrin receptor alpha(v)beta3 was determined by immunohistochemistry.
Osteopontin mRNA was expressed de novo in the peri-infarct region from 3 to 48 hours; by 5 days osteopontin mRNA expression was restricted to the infarct. Osteopontin protein was expressed by peri-infarct microglia beginning at 24 hours and by microglia/macrophages at 48 hours in the infarct. Integrin receptor alpha(v)beta3 was expressed in peri-infarct astrocytes at 5 and 15 days.
Early microglial/macrophage expression of osteopontin mRNA defines the borders and final infarct area at 24 hours. At 5 days osteopontin ligand is at a distance from the peri-infarct astrocytes expressing integrin receptor alpha(v)beta3. By 15 days astrocytes expressing integrin receptor alpha(v)beta3 are localized in an osteopontin-rich region concomitant with formation of the new glial-limiting membrane. The de novo expression and interaction of osteopontin ligand with its receptor integrin alpha(v)beta3 suggest a role in wound healing after focal stroke.
局灶性脑卒中发生后，梗死灶周围区域的小胶质细胞和星形胶质细胞被激活。激活的胶质细胞的一项关键功能是形成保护性屏障，最终形成新的胶质界膜。骨桥蛋白是一种在伤口愈合过程中表达的临时基质蛋白，在局灶性脑卒中后被诱导表达。本研究旨在确定骨桥蛋白及其整合素受体α(v)β3在梗死灶周围胶质瘢痕屏障形成及随后新的胶质界膜形成过程中的时空表达情况。
将19只自发性高血压大鼠进行大脑中动脉永久性闭塞，并在闭塞后3、6和24小时以及2、5和15天处死。通过原位杂交确定骨桥蛋白mRNA的时空表达，通过免疫组织化学确定骨桥蛋白配体及其整合素受体α(v)β3的时空表达。
骨桥蛋白mRNA在梗死灶周围区域于3至48小时开始重新表达；到5天时，骨桥蛋白mRNA表达局限于梗死灶。骨桥蛋白蛋白在梗死灶周围的小胶质细胞中于24小时开始表达，在梗死灶中的小胶质细胞/巨噬细胞中于48小时开始表达。整合素受体α(v)β3在5天和15天时在梗死灶周围的星形胶质细胞中表达。
骨桥蛋白mRNA早期在小胶质细胞/巨噬细胞中的表达在24小时时界定了边界和最终梗死面积。在5天时，骨桥蛋白配体与表达整合素受体α(v)β3的梗死灶周围星形胶质细胞有一定距离。到15天时，表达整合素受体α(v)β3的星形胶质细胞位于富含骨桥蛋白的区域，同时新的胶质界膜形成。骨桥蛋白配体的从头表达及其与受体整合素α(v)β3的相互作用提示其在局灶性脑卒中后的伤口愈合中发挥作用。
