NEURONAL PROTECTION FROM CEREBRAL-ISCHEMIA BY SYNTHETIC FIBRONECTIN PEPTIDES TO LEUKOCYTE ADHESION MOLECULES

Leukocytes play an important role in the development of ischemia/reper fusion injury. Recent work in our laboratory has demonstrated that a m ixture of synthetic fibronectin peptides to leukocyte adhesion molecul es reduces ischemic brain damage after transient focal cerebral ischem ia. The purpose of this study was to evaluate the efficacy of the indi vidual peptides on leukocyte accumulation, infarct size, and neurologi cal outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Thirty-five animals were divided into five groups: transi ent ischemia without treatment (Group I), treatment with arginyl-glycy l-aspartic acid (RGD) peptide (Group II), connecting segment (CS)-1 pe ptide (Group III), fibronectin (FN)-C/H-V peptide (Group TV), and scra mbled FN-C/H-V peptide (Group V). Groups III and IV showed a significa nt decrease in the degree of leukocyte infiltration in the lesion and in the infarct size (p < 0.05) when compared to Groups II II, and V. T he neurological grade of Groups III and IV was significantly better th an in Groups I, II, and V at 48 h after repel-fusion (p < 0.01). Thus, in addition to demonstrating the potential efficacy of synthetic pept ides as therapeutic agents for ischemia-reperfusion, these results als o offer new insights into the mechanisms of leukocyte arrest and recru itment in ischemia/reperfusion injury.