Article

Journal of Cerebral Blood Flow & Metabolism (1996) 16, 1120–1125; doi:10.1097/00004647-199611000-00005

Neuronal Protection from Cerebral Ischemia by Synthetic Fibronectin Peptides to Leukocyte Adhesion Molecules

Kiyoyuki Yanaka, Paul J Camarata, Stephen R Spellman, James B McCarthy*, Leo T Furcht*, Walter C Low and Roberto C Heros

  1. Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota, U.S.A.
  2. *Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, U.S.A.

Correspondence: Paul J Camarata, Neurology/Neurosurgery, P.C., 4440 Broadway, Kansas City, MO 64111, U.S.A.

Received 7 February 1996; Revised 9 May 1996; Accepted 13 May 1996.

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Abstract

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.

Keywords:

Adhesion molecules, Cerebral ischemia, Fibronectin, Leukocytes, Rats, Reperfusion

Abbreviations:

ANOVA, analysis of variance; CCA, common carotid artery; CNS, central nervous system; CS, connecting segment; ECA, external carotid artery; FN, fibronectin; HPLC, high-performance liquid chromatography; ICA, internal carotid artery; ICAM, intercellular adhesion molecule; MCA, middle carotid artery; MPO, myeloperoxidase; PMN, polymorphonuclear leukocyte; RGD, arginyl-glycyl-aspartic acid; SC-V, scrambled version; TTC, triphenyl-2H-tetragaolim; VCAM, vascular cell adhesion molecule; VLA, very late antigen

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