ArticlePloS one2019
Poly-arginine-18 peptides do not exacerbate bleeding, or improve functional outcomes following collagenase-induced intracerebral hemorrhage in the rat.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Translational Intracerebral Hemorrhage Research: Has Current Neuroprotection Research ARRIVEd at a Standard for Experimental Design and Reporting?Translational stroke research · 2020Pooled it
- Pharmacokinetics and Neuroprotective Efficacy of Poly-Arginine Peptide R18D in Sprague Dawley Rats Subjected to Transient Intraluminal Filament Middle Cerebral Artery Occlusion Stroke.CNS neuroscience & therapeutics · 2026Article
- Enhanced precision in intracerebral hemorrhage modeling via methodological improvements and outcomes.Scientific reports · 2025Article
- Animal models for the study of intracranial hematomas (Review).Experimental and therapeutic medicine · 2023Review
- Early, Intense Rehabilitation Fails to Improve Outcome After Intra-Striatal Hemorrhage in Rats.Neurorehabilitation and neural repair · 2022Article
- The role of L-arginine metabolism in neurocritical care patients.Neural regeneration research · 2022Review
- Intrathecal and systemic alterations of L-arginine metabolism in patients after intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Behavioral Assessment of Sensory, Motor, Emotion, and Cognition in Rodent Models of Intracerebral Hemorrhage.Frontiers in neurology · 2021Review
- Advances in D-Amino Acids in Neurological Research.International journal of molecular sciences · 2020Review
- Neuroprotective Cationic Arginine-Rich Peptides (CARPs): An Assessment of Their Clinical Safety.Drug safety · 2020Review
- Infusion of Cold Saline into the Carotid Artery Does Not Affect Outcome After Intrastriatal Hemorrhage.Therapeutic hypothermia and temperature management · 2020Article
- Assessment of recombinant tissue plasminogen activator (rtPA) toxicity in cultured neural cells and subsequent treatment with poly-arginine peptide R18D.Neurochemical research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCationic arginine-rich peptides (CARPs) have demonstrated neuroprotective and/or behavioural efficacy in ischemic and hemorrhagic stroke and traumatic brain injury models. Therefore, in this study we investigated the safety and neuroprotective efficacy of the CARPs poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer R18D given in the acute bleeding phase in an intracerebral hemorrhage (ICH) model.
methodsOne hundred and fifty-eight male Sprague-Dawley rats received collagenase-induced ICH. Study 1 examined various doses of R18D (30, 100, 300, or 1000 nmol/kg) or R18 (100, 300, 1000 nmol/kg) administered intravenously 30 minutes post-collagenase injection on hemorrhage volume 24 hours after ICH. Study 2 examined R18D (single intravenous dose) or R18 (single intravenous dose, plus 6 daily intraperitoneal doses) at 300 or 1000 nmol/kg commencing 30 minutes post-collagenase injection on behavioural outcomes (Montoya staircase test, and horizontal ladder test) in the chronic post-ICH period. A histological assessment of tissue loss was assessed using a Nissl stain at 28 days after ICH.
resultsWhen administered during ongoing bleeding, neither R18 or R18D exacerbated hematoma volume or worsened functional deficits. Lesion volume assessment at 28 days post-ICH was not reduced by the peptides; however, animals treated with the lower R18D 300 nmol/kg dose, but not with the higher 1000 nmol/kg dose, demonstrated a statistically increased lesion size compared to saline treated animals.
conclusionOverall, both R18 and R18D appeared to be safe when administered during a period of ongoing bleeding following ICH. Neither peptide appears to have any statistically significant effect in reducing lesion volume or improving functional recovery after ICH. Additional studies are required to further assess dose efficacy and safety in pre-clinical ICH studies.
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