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(Stroke. 1998;29:1698-1707.)
© 1998 American Heart Association, Inc.

Original Contributions

Osteopontin and its Integrin Receptor _vß₃ Are Upregulated During Formation of the Glial Scar After Focal Stroke

Julie A. Ellison, PhD; James J. Velier, PhD; Patricia Spera, PhD; Zdenka L. Jonak, PhD; Xinkang Wang, PhD; Frank C. Barone, PhD; Giora Z. Feuerstein, MD

From the Departments of Cardiovascular Pharmacology and Molecular and Cellular Immunology (Z.L.J.), SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.

Correspondence to Giora Z. Feuerstein, MD, Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd, PO Box 1539, UW2523, King of Prussia, PA 19406. E-mail G_Z_Feuerstein{at}SBPHRD.COM

Background and Purpose—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 _vß₃ during formation of the peri-infarct gliotic barrier and subsequent formation of a new glial-limiting membrane.

Methods—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 _vß₃ was determined by immunohistochemistry.

Results—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 _vß₃ was expressed in peri-infarct astrocytes at 5 and 15 days.

Conclusions—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 _vß₃. By 15 days astrocytes expressing integrin receptor _vß₃ 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 _vß₃ suggest a role in wound healing after focal stroke.

Editorial Comment

Takeo Abumiya, MD, Guest Editor; Gregory J. del Zoppo, MD,Guest Editor

Department Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif

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