Antagonism of leukocyte adherence by synthetic fibronectin peptide V in a rat model of transient focal cerebral ischemia.
OBJECTIVE
Activated polymorphonuclear leukocytes (PMNs) seem to be directly involved in potentiating ischemic brain injury. Recent work in our laboratory demonstrated that synthetic fibronectin peptides significantly inhibit PMN accumulation in ischemic tissue, reduce the size of infarction, and reduce neurological dysfunction after transient focal cerebral ischemia in rats. The purpose of this study was to examine any dose-related effects (Experiment 1) and the optimal timing of the administration (Experiment 2) of synthetic fibronectin peptide V (FN-C/H-V) to further substantiate the role of the peptide in ameliorating cerebral ischemic damage.


METHODS
Fifty-six animals were included in the study. We evaluated the efficacy of FN-C/H-V on PMN accumulation in ischemic tissue, infarct size, and neurological outcomes in rats subjected to 1 hour of cerebral ischemia and 48 hours of reperfusion.


RESULTS
In Experiment 1, the animals receiving FN-C/H-V at a dose of 10 to 15 mg/kg of body weight per injection showed significant reduction of PMN accumulation, reduction of infarct size, and improvement of neurological outcomes at 48 hours after reperfusion compared to untreated animals (P < 0.05). In Experiment 2, the animals receiving FN-C/H-V within 3 hours after reperfusion also showed significantly better results than untreated animals (P < 0.05). Despite the treatment delay, the administration of FN-C/H-V inhibited PMN accumulation after reperfusion but did not reduce the size of infarction when administered 6 hours after reperfusion.


CONCLUSIONS
These data suggest that relatively late postischemic administration of FN-C/H-V is effective in brain protection after ischemia/reperfusion.
Yanaka
K
K
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, USA.
Camarata
P J
PJ
Spellman
S R
SR
McCarthy
J B
JB
Furcht
L T
LT
Low
W C
WC
D000818:Animals; D001925:Brain Damage, Chronic / Q000276:immunology; D002544:Cerebral Infarction / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000276:immunology*; D007957:Leukocyte Adherence Inhibition Test; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D009460:Neurologic Examination / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology
D005353:Fibronectins; D010446:Peptide Fragments; D009195:Peroxidase