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(Stroke. 2004;35:1158.)
© 2004 American Heart Association, Inc.

Original Contributions

Cerebral Endothelial Expression of Adhesion Molecules in Mice with Chronic Graft-Versus-Host Disease

Petra Sostak, MD; Petra Reich, MD; Claudio S. Padovan, MD; Armin Gerbitz, MD; Ernst Holler, MD Andreas Straube, MD

From the Departments of Neurology (P.S., P.R., C.S.P., A.S.) and Internal Medicine III (A.G.), Klinikum Großhadern, Ludwig-Maximilians-University, Munich; and the Department of Hematology and Oncology (E.H.), University of Regensburg, Regensburg, Germany.

Correspondence to Petra Sostak, MD, Department of Neurology, Klinikum Großhadern, Marchioninistr 15, 81377 Munich, Germany. E-mail Petra.Sostak{at}nro.med.uni-muenchen.de

Background and Purpose— Graft-versus-host disease (GvHD) is a major complication after allogeneic bone marrow transplantation (BMT). The theory that the central nervous system (in addition to the peripheral nervous system) participates in GvHD has been supported by detection of cerebral lymphomononuclear infiltrates in experimental GvHD and the observation of cerebral angiitis-like disease in patients with chronic GvHD.

Methods— In a murine BMT model, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on cerebral endothelium after allogeneic and syngeneic transplantation. Through the use of ICAM-1–knockout mice, the effect of ICAM-1 deficiency on cellular infiltration was evaluated. As an indicator of enhanced apoptotic cell death, we examined the cerebral expression of Fas antigen (Fas), the occurrence of the poly-ADP ribose polymerase p85 fragment, and the distribution of TUNEL positive–stained cells.

Results— In close correlation with earlier findings of cerebral infiltration in the same animals, we found cerebral endothelial upregulation of ICAM-1 and especially of VCAM-1 in allogeneic recipients compared with syngeneic animals without GvHD and unmanipulated controls. In ICAM-1–knockout mice, leukocytic infiltration did not differ from that in wild-type animals. Neither cerebral histopathologic changes nor an apoptotic effect of cellular infiltrates on brain parenchyma could be detected.

Conclusions— In this model of experimental GvHD, VCAM-1 may play a critical role in leukocyte recruitment into the central nervous system of animals with chronic GvHD.

Key Words: immunohistochemistry • cerebrovascular disorders • endothelium, vascular • graft-versus-host disease • cell adhesion molecules