Synthetic fibronectin peptide exerts neuroprotective effects on transient focal brain ischemia in rats.
Leukocytes have been investigated during the past decade for their roles in secondary tissue damage after ischemia/reperfusion injury. Peptide PRARIY, a synthetic fibronectin peptide, has shown an anti-adhesion effect in in vitro studies. Previous studies have demonstrated that anti-adhesion agents lead to reductions in apoptosis. The purpose of the present study was to determine whether the peptide PRARIY displays anti-inflammatory, anti-apoptotic, and neuroprotective effects following transient focal brain ischemia in rats. Twenty-six male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: phosphate-buffered saline (PBS) controls, PRARI controls, and PRARIY treatments. The right middle cerebral artery was transiently occluded using a 4-0 nylon suture. One hour later, the occluder was withdrawn, and reperfusion was maintained for 48 h. Immediately after reperfusion, the peptides (20 mg/kg, dissolved in PBS) and the same volume of PBS were continuously infused through the right external carotid artery using an osmotic minipump for 24 h. Neurological deficits were examined at 3, 24, and 48 h after ischemia. Forty-eight hours after reperfusion, the rats were sacrificed for determining infarction size, leukocyte infiltration, and apoptosis in the ischemia area. Unexpectedly, PRARIY did not influence leukocyte infiltration. However, PRARIY-treated rats showed significantly functional outcome, reduction of infarction size, decrease of TUNEL positive cells, and increase of Bcl-2 (anti-apoptotic protein) positive cells in the ischemic areas when compared to the controls. These data indicate that the peptide PRARIY exerts its neuroprotective effects via supporting neural cell survival rather than anti-leukocyte recruitment following brain ischemia/reperfusion injury.
Zhao
Li Ru
LR
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA. lzhao@lsuhsc.edu
Spellman
Steve
S
Kim
Jonggul
J
Duan
Wei-Ming
WM
McCarthy
James B
JB
Low
Walter C
WC
D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D002545:Brain Ischemia / Q000517:prevention & control*; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005353:Fibronectins / Q000138:chemical synthesis / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D010455:Peptides / Q000138:chemical synthesis / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005353:Fibronectins; D018696:Neuroprotective Agents; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D009195:Peroxidase