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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-7-1
pubmed:abstractText
The selectin family of adhesion molecules is involved in adhesion of leukocyte to microcirculatory system and the transmigration into brain parenchyma. Although the role of P-selectin may be important in the pathogenesis of brain ischemia, a possible protective effect on ischemic brain injury by blocking P-selectin has not been reported. We have examined the effects of a novel anti-P-selectin antibody on ischemic brain injury after 24 h of permanent middle cerebral artery occlusion (MCAO) in rat. Male Wistar rats were subjected to MCAO by an insertion of a silicone rubber cylinder for 24 h. Anti-rat P-selectin monoclonal antibody, ARP 2-4, was injected intravenously at a dose of 1 mg kg-1 at 5 min before the induction of MCAO. Control animals received the same volume of vehicle solution. Regional cerebral blood flow (rCBF) was measured immediately after and at 8 h of MCAO. At decapitation of rats at 24 h of permanent MCAO, infarct size was compared between the antibody and vehicle treated group. In addition, immunohistochemistry for leukocyte infiltration and HSP72, and histochemistry for TUNEL were also, compared. Pretreatment with ARP 2-4 improved rCBF at 8 h of MCAO (55.4% +/- 11.7% of control, n = 5) as compared to vehicle group (24.2% +/- 11.8%, n = 5, p < 0.02). Although leukocyte infiltration was not normally detected by monoclonal antibodies for CD11a and CD18, it became remarkably evident at 1 day of MCAO. Although HSP72 and TUNEL were not also detected in sham control brains, they were induced in neurons of the MCA area at 1 day of MCAO. Treatment with ARP 2-4 significantly reduced the numbers of leukocyte and neurons with positive HSP72 and TUNEL stainings. These results demonstrated that an administration of a monoclonal antibody against P-selectin improved rCBF, and attenuated infarct size that was associated with reduction of leukocyte infiltration. Furthermore, treatment with the antibody reduced both HSP72 and TUNEL stainings. These data suggest an important role of P-selectin in ischemic brain damage, and a future therapeutic potential to human stroke patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0161-6412
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
269-76
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10319335-Animals, pubmed-meshheading:10319335-Antibodies, Monoclonal, pubmed-meshheading:10319335-Apoptosis, pubmed-meshheading:10319335-Arterial Occlusive Diseases, pubmed-meshheading:10319335-Brain Ischemia, pubmed-meshheading:10319335-Cerebral Cortex, pubmed-meshheading:10319335-Cerebral Infarction, pubmed-meshheading:10319335-Cerebrovascular Circulation, pubmed-meshheading:10319335-Disease Models, Animal, pubmed-meshheading:10319335-HSP72 Heat-Shock Proteins, pubmed-meshheading:10319335-Heat-Shock Proteins, pubmed-meshheading:10319335-In Situ Nick-End Labeling, pubmed-meshheading:10319335-Leukocytes, pubmed-meshheading:10319335-Lymphocyte Function-Associated Antigen-1, pubmed-meshheading:10319335-Male, pubmed-meshheading:10319335-P-Selectin, pubmed-meshheading:10319335-Rats, pubmed-meshheading:10319335-Rats, Wistar
pubmed:year
1999
pubmed:articleTitle
Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat.
pubmed:affiliation
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't