title: Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain.
abstract: We tested the hypothesis that treatment of transient focal cerebral ischemia in rat with antibodies directed against adhesion molecules reduces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon monofilament into the internal carotid artery. Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellular adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, animals were killed and the brains analyzed for ischemic cell damage, using hematoxylin and eosin (H/E); apoptosis, using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant reduction in the volume of infarction (p < 0.01) and a decline in the absolute (p < 0.001), and normalized (to the ischemic areas, p < 0.05) numbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immunoreactive MPO cells were also reduced in the treatment groups compared to those in the control group (p < 0.05). These data suggest that treatment with anti-adhesion molecule antibodies selectively reduce apoptosis, and that a contributing factor to the beneficial effect of antibody treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.
authors.affiliation: Neurology Department, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chopp
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Jiang
authors.forename: R L
authors.initials: RL
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Prostak
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002452:Cell Count; D002561:Cerebrovascular Disorders / Q000473:pathology / Q000503:physiopathology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D009195:Peroxidase