title: Poly-arginine peptides reduce infarct volume in a permanent middle cerebral artery rat stroke model.
abstract: We recently reported that poly-arginine peptides have neuroprotective properties both in vitro and in vivo. In cultured cortical neurons exposed to glutamic acid excitotoxicity, we demonstrated that neuroprotective potency increases with polymer length plateauing at R15 to R18 (R = arginine resides). In an in vivo study in rats, we also demonstrated that R9D (R9 peptide synthesised with D-isoform amino acids) administered intravenously at a dose of 1000 nmol/kg 30 min after permanent middle cerebral artery occlusion (MCAO) reduces infarct volume. Based on these positive in vitro and in vivo findings, we decided to examine the neuroprotective efficacy of the L-isoform poly-arginine peptides, R12, R15 and R18 when administered at a dose of 1000 nmol/kg 30 min after permanent MCAO in the rat.
  
  
  
  At 24 h post-MCAO, there was reduced total infarct volume for R12 (12.8 % reduction) and R18 (20.5 % reduction), but this reduction only reached statistical significance for R18. Brain slice analysis revealed significantly reduced injury in coronal slices 4 and 5 for R18, and slice 5 for R12. The R15 peptide had no effect on infarct volume. Peptide treatment did not reveal any statistical significant improvement in functional outcomes.
  
  
  
  While these findings confirm the in vivo neuroprotective properties of poly-arginine peptides, additional dose studies are required particularly in less severe transient MCAO models so as to further assess the potential of these agents as a stroke therapy.
authors.affiliation: Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA, Australia.|Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia.|School of Heath Sciences, The University of Notre Dame Australia, Fremantle, WA, Australia.
authors.forename: Diego
authors.initials: D
authors.lastname: Milani
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Australia.|Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA, Australia.|Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia.
authors.forename: Vince W
authors.initials: VW
authors.lastname: Clark
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Australia.|Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA, Australia.|Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Cross
authors.affiliation: Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia.|School of Heath Sciences, The University of Notre Dame Australia, Fremantle, WA, Australia.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Anderton
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Australia.|Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA, Australia.|Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia.
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Australia. bruno.meloni@wanri.uwa.edu.au.|Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA, Australia. bruno.meloni@wanri.uwa.edu.au.|Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia. bruno.meloni@wanri.uwa.edu.au.
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D045442:Rotarod Performance Test; D012720:Severity of Illness Index; D015431:Weight Loss / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; C015462:polyarginine
keywords: Middle cerebral artery occlusion; Neuroprotection; Poly-arginine peptides; Stroke