Neuronal protection from cerebral ischemia by synthetic fibronectin peptides to leukocyte adhesion molecules.
Leukocytes play an important role in the development of ischemia/reperfusion injury. Recent work in our laboratory has demonstrated that a mixture of synthetic fibronectin peptides to leukocyte adhesion molecules reduces ischemic brain damage after transient focal cerebral ischemia. The purpose of this study was to evaluate the efficacy of the individual peptides on leukocyte accumulation, infarct size, and neurological outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Thirty-five animals were divided into five groups: transient ischemia without treatment (Group I), treatment with arginyl-glycyl-aspartic acid (RGD) peptide (Group II), connecting segment (CS)-1 peptide (Group III), fibronectin (FN)-C/H-V peptide (Group IV), and scrambled FN-C/H-V peptide (Group V). Groups III and IV showed a significant decrease in the degree of leukocyte infiltration in the lesion and in the infarct size (p < 0.05) when compared to Groups I, II, and V. The neurological grade of Groups III and IV was significantly better than in Groups I, II, and V at 48 h after reperfusion (p < 0.01). Thus, in addition to demonstrating the potential efficacy of synthetic peptides as therapeutic agents for ischemia-reperfusion, these results also offer new insights into the mechanisms of leukocyte arrest and recruitment in ischemia/reperfusion injury.
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, USA.
K
K
Yanaka
P J
PJ
Camarata
S R
SR
Spellman
J B
JB
McCarthy
L T
LT
Furcht
W C
WC
Low
R C
RC
Heros
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D010455:Peptides