Document Detail


Prevention of vasospasm by anti-CD11/CD18 monoclonal antibody therapy following subarachnoid hemorrhage in rabbits.
MedLine Citation:
PMID:  15255256     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Adhesion of leukocytes and their migration into the periadventitial space may be critical in the pathophysiology of vasospasm following subarachnoid hemorrhage (SAH). The cell adhesion molecules involved in this process are lymphocyte function-associated antigen-1 (CD11a/CD18) and macrophage antigen-1 (CD11b/CD18), which are present on neutrophils/macrophages, and intercellular adhesion molecule-1 (CD54), which is present in endothelial cells. A humanized monoclonal antibody (mAb), Hu23F2G, targets CD11/CD18 and prevents leukocyte adhesion to endothelial cells. In this study, systemic administration of Hu23F2G prevented vasospasm in the rabbit model of SAH. METHODS: Twenty-six New Zealand White rabbits were injected with autologous blood into the cisterna magna to induce SAH, after which they were randomized to receive injections of either Hu23F2G (10 animals) or a placebo at 30 minutes and 24 and 48 hours after SAH (six animals). Control animals underwent sham operations (four animals) or SAH alone (six animals). The animals were killed 72 hours after SAH, their bodies perfused and fixed, and their basilar arteries processed for morphometric analysis. Peripheral white blood cells (WBCs) were counted at 72 hours. The percentages of lumen patency were compared using the Student t-test. The presence of neutrophils and macrophages was confirmed by immunohistochemical analysis in which a rat anti-rabbit anti-CD18 mAb and cresyl violet were used. Treatment with Hu23F2G resulted in the significant prevention of vasospasm. Animals treated with Hu23F2G had 90 +/- 7% lumen patency compared with 65 +/- 7% in the placebo group (p = 0.025). The percentage of lumen patency in the SAH-only group was 59 +/- 10%. The mean WBC count was 16,300 +/- 2710/microl in the treatment group, compared with 7000 +/- 386/microl in the control group (p = 0.02). Administration of Hu23F2G produced increased numbers of WBCs in 70% of the animals treated. CONCLUSIONS: This study supports the concept that leukocyte-endothelial cell interactions play an important role in the pathophysiology of chronic vasospasm after SAH. Systemic therapy with an anti-CD11/CD18 mAb prevents vasospasm after SAH by inhibiting adhesion of neutrophils and macrophages and their migration into the periadventitial space.
Authors:
Gustavo Pradilla; Paul P Wang; Federico G Legnani; Lynn Ogata; Gregory N Dietsch; Rafael J Tamargo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  101     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-16     Completed Date:  2004-09-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-92     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacology*,  therapeutic use
Basilar Artery / drug effects
Disease Models, Animal
Leukocyte Count
Rabbits
Subarachnoid Hemorrhage / blood,  complications*
Vascular Patency / drug effects*
Vasospasm, Intracranial / blood,  etiology*,  prevention & control*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/HU23F2G

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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