Poly-Arginine Peptides R18 and R18D Improve Functional Outcomes After Endothelin-1-Induced Stroke in the Sprague Dawley Rat

Bruno P. Meloni, Samantha M. South, Daphne A. Gill, Amber L. Marriott, Robert A. Déziel, Angela Jacques, David J. Blacker, Neville W. Knuckey

Research output: Contribution to journalArticle

Abstract

We have previously demonstrated that R18 and its d-enantiomer, R18D, are neuroprotective at 24 hours following intraluminal filament occlusion of the middle cerebral artery (MCAO) in the rat. This study examined R18 and R18D effectiveness in improving functional outcomes at up to 56 days poststroke following endothelin-1-induced MCAO. Peptides were administered intravenously at doses of 100, 300, or 1000 nmol/kg, 60 minutes after MCAO. Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c), a neuroprotective currently in phase 3 clinical stroke trials, was used as a benchmark. The study demonstrated that R18 (300 and 1000 nmol/kg) was the most effective peptide in improving functional outcomes, followed by R18D (300 and 1000 nmol/kg), and NA-1 (300 and 100 nmol/kg). Furthermore, R18 at doses of 300 and 1000 nmol/kg was the most effective agent in restoring pre-stroke body weight, while R18 and R18D at doses of 300 and 1000 nmol/kg, but not NA-1 also significantly reduced the number of animals requiring hand feeding 48 hours after stroke. This study confirms that R18 and R18D are effective in improving long-term functional outcomes after stroke, and suggests that R18 may be more effective than NA-1.

Original languageEnglish
Pages (from-to)426-435
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume78
Issue number5
DOIs
Publication statusPublished - 1 May 2019

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Endothelin-1
Sprague Dawley Rats
Arginine
Stroke
Benchmarking
Phase III Clinical Trials
Peptides
Forelimb
Middle Cerebral Artery Infarction
Hand
Body Weight
R18 peptide

Cite this

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title = "Poly-Arginine Peptides R18 and R18D Improve Functional Outcomes After Endothelin-1-Induced Stroke in the Sprague Dawley Rat",
abstract = "We have previously demonstrated that R18 and its d-enantiomer, R18D, are neuroprotective at 24 hours following intraluminal filament occlusion of the middle cerebral artery (MCAO) in the rat. This study examined R18 and R18D effectiveness in improving functional outcomes at up to 56 days poststroke following endothelin-1-induced MCAO. Peptides were administered intravenously at doses of 100, 300, or 1000 nmol/kg, 60 minutes after MCAO. Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c), a neuroprotective currently in phase 3 clinical stroke trials, was used as a benchmark. The study demonstrated that R18 (300 and 1000 nmol/kg) was the most effective peptide in improving functional outcomes, followed by R18D (300 and 1000 nmol/kg), and NA-1 (300 and 100 nmol/kg). Furthermore, R18 at doses of 300 and 1000 nmol/kg was the most effective agent in restoring pre-stroke body weight, while R18 and R18D at doses of 300 and 1000 nmol/kg, but not NA-1 also significantly reduced the number of animals requiring hand feeding 48 hours after stroke. This study confirms that R18 and R18D are effective in improving long-term functional outcomes after stroke, and suggests that R18 may be more effective than NA-1.",
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Poly-Arginine Peptides R18 and R18D Improve Functional Outcomes After Endothelin-1-Induced Stroke in the Sprague Dawley Rat. / Meloni, Bruno P.; South, Samantha M.; Gill, Daphne A.; Marriott, Amber L.; Déziel, Robert A.; Jacques, Angela; Blacker, David J.; Knuckey, Neville W.

In: Journal of Neuropathology and Experimental Neurology, Vol. 78, No. 5, 01.05.2019, p. 426-435.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Poly-Arginine Peptides R18 and R18D Improve Functional Outcomes After Endothelin-1-Induced Stroke in the Sprague Dawley Rat

AU - Meloni, Bruno P.

AU - South, Samantha M.

AU - Gill, Daphne A.

AU - Marriott, Amber L.

AU - Déziel, Robert A.

AU - Jacques, Angela

AU - Blacker, David J.

AU - Knuckey, Neville W.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - We have previously demonstrated that R18 and its d-enantiomer, R18D, are neuroprotective at 24 hours following intraluminal filament occlusion of the middle cerebral artery (MCAO) in the rat. This study examined R18 and R18D effectiveness in improving functional outcomes at up to 56 days poststroke following endothelin-1-induced MCAO. Peptides were administered intravenously at doses of 100, 300, or 1000 nmol/kg, 60 minutes after MCAO. Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c), a neuroprotective currently in phase 3 clinical stroke trials, was used as a benchmark. The study demonstrated that R18 (300 and 1000 nmol/kg) was the most effective peptide in improving functional outcomes, followed by R18D (300 and 1000 nmol/kg), and NA-1 (300 and 100 nmol/kg). Furthermore, R18 at doses of 300 and 1000 nmol/kg was the most effective agent in restoring pre-stroke body weight, while R18 and R18D at doses of 300 and 1000 nmol/kg, but not NA-1 also significantly reduced the number of animals requiring hand feeding 48 hours after stroke. This study confirms that R18 and R18D are effective in improving long-term functional outcomes after stroke, and suggests that R18 may be more effective than NA-1.

AB - We have previously demonstrated that R18 and its d-enantiomer, R18D, are neuroprotective at 24 hours following intraluminal filament occlusion of the middle cerebral artery (MCAO) in the rat. This study examined R18 and R18D effectiveness in improving functional outcomes at up to 56 days poststroke following endothelin-1-induced MCAO. Peptides were administered intravenously at doses of 100, 300, or 1000 nmol/kg, 60 minutes after MCAO. Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c), a neuroprotective currently in phase 3 clinical stroke trials, was used as a benchmark. The study demonstrated that R18 (300 and 1000 nmol/kg) was the most effective peptide in improving functional outcomes, followed by R18D (300 and 1000 nmol/kg), and NA-1 (300 and 100 nmol/kg). Furthermore, R18 at doses of 300 and 1000 nmol/kg was the most effective agent in restoring pre-stroke body weight, while R18 and R18D at doses of 300 and 1000 nmol/kg, but not NA-1 also significantly reduced the number of animals requiring hand feeding 48 hours after stroke. This study confirms that R18 and R18D are effective in improving long-term functional outcomes after stroke, and suggests that R18 may be more effective than NA-1.

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KW - NA-1

KW - Neuroprotection

KW - Poly-arginine peptides

KW - R18

KW - Stroke

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DO - 10.1093/jnen/nlz014

M3 - Article

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EP - 435

JO - Journal of Neuropathology and Experimental Neurology

JF - Journal of Neuropathology and Experimental Neurology

SN - 0022-3069

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