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.
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During 24-72 h of reperfusion is when most brain leukocyte infiltration occurs.
“During 24–72 h of reperfusion is when most brain leukocyte infiltration occurs (Chatzipanteli et al., 2000; Chopp et al., 1996; Matsuo et al., 1994; Royo et al., 1999).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Chopp et al., 1996
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- Authors
- Chopp, M., Li, Y., Jiang, N., Zhang, R. L., & Prostak, J.
- Affiliations
- Henry Ford Health (US)
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 1996-07
- Volume
- 16
- Issue
- 4
- Pages
- 578-584
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2056824541
- Cited by
- 185
- References
- 76
- Citations by year
- 2025: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 6 · 2012: 3
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hort Innovation
- National Institutes of Health (5r01ns034184-04, 5r01ns033627-08)
- National Institute of Neurological Disorders and Stroke (R01NS-33627, P01NS023393, R01NS-34184)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- adhesion molecules, apoptosis, transient middle cerebral artery occlusion, focal cerebral ischemia, ICAM-1, CD11b/CD18 integrin, infarct size, ischemia-reperfusion injury, neuroprotection
- MeSH terms
- Animals, Antibodies, Monoclonal, Arterial Occlusive Diseases, Brain, Cell Count, Cerebrovascular Disorders, Male, Peroxidase, Cell Adhesion Molecules, Macrophage-1 Antigen, Apoptosis, Rats
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