Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice.
Cerebral ischemia triggers an inflammatory process involving the infiltration of leukocytes to the parenchyma. Circulating leukocytes adhere to the vascular wall through adhesion molecules. Here we quantified the in vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in the brain, heart and lungs from 6 to 48 h after transient middle cerebral artery (MCA) occlusion in rats, by intravenous injection of a tracer radiolabelled anti-VCAM-1 antibody. The vascular localization of VCAM-1 was verified by immunohistochemistry after in vivo injection of the antibody. Vascular cell adhesion molecule-1 was strongly induced (4-fold at 24 h) in the microvasculature of the ischemic area, and, to a lesser extent, in the contralateral hemisphere and in a remote organ, the heart, but not in the lungs, indicating that the inflammatory process propagates beyond the injured brain. We injected intravenously either blocking doses of anti-VCAM-1 antibodies or control antibodies after MCA occlusion in rats and mice. We evaluated the neurological score in rats, and infarct volume at 2 days in rats and at 4 days in mice. Anti-VCAM-1 did not protect against ischemic damage either in rats or in mice. Vascular cell adhesion molecule-1 blockade significantly decreased the number of ED1 (labeling monocytes /macrophages/reactive microglia)-positive cells in the ischemic rat brain. However, it did not reduce the numbers of infiltrating neutrophils and lymphocytes, and total leukocytes (CD45 positive), which showed a trend to increase. The results show vascular upregulation of VCAM-1 after transient focal ischemia, but no benefits of blocking VCAM-1, suggesting that this is not a therapeutical strategy for stroke treatment.
Justicia
Carles
C
Department of Pharmacology and Toxicology, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
Martín
Abraham
A
Rojas
Santiago
S
Gironella
Meritxell
M
Cervera
Alvaro
A
Panés
Julián
J
Chamorro
Angel
A
Planas
Anna M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1