Poly-arginine peptides reduce infarct volume in a permanent middle cerebral artery rat stroke model

BMC Neuroscience

Research Article

Jane L. Cross¹  Vince W. Clark¹  Bruno P. Meloni¹  Neville W. Knuckey¹  Diego Milani²  Ryan S. Anderton³ 

[1] 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, 6009, Nedlands, WA, 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, 6009, Nedlands, WA, Australia;School of Heath Sciences, The University of Notre Dame Australia, Fremantle, WA, Australia;Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, 6009, Nedlands, WA, Australia;School of Heath Sciences, The University of Notre Dame Australia, Fremantle, WA, Australia;

关键词: Poly-arginine peptides;    Middle cerebral artery occlusion;    Stroke;    Neuroprotection;   

DOI  :  10.1186/s12868-016-0253-z

 received in 2016-01-09, accepted in 2016-04-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundWe 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.ResultsAt 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.ConclusionWhile 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.

【 授权许可】

CC BY   
© Milani et al. 2016