Poly-arginine-18 peptides do not exacerbate bleeding, or improve functional outcomes following collagenase-induced intracerebral hemorrhage in the rat


Autoři: Lane Liddle aff001;  Ryan Reinders aff001;  Samantha South aff002;  David Blacker aff003;  Neville Knuckey aff003;  Frederick Colbourne aff001;  Bruno Meloni aff003
Působiště autorů: Department of Psychology, University of Alberta, Edmonton, Alberta, Canada aff001;  Office of Research Enterprise, The University of Western Australia, Western Australia, Australia aff002;  Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia aff003;  Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, Western Australia, Australia aff004;  Department of Neurology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia aff005;  Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia aff006;  Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada aff007
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224870

Souhrn

Background

Cationic 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.

Methods

One 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.

Results

When 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.

Conclusion

Overall, 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.

Klíčová slova:

Brain damage – Collagenases – Hemorrhagic stroke – Histology – Ischemic stroke – Rats – Carps


Zdroje

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