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

Autor: Ryan Reinders, Samantha M South, Bruno P. Meloni, Neville W. Knuckey, Lane J Liddle, David Blacker, Frederick Colbourne
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Hydrolases
medicine.medical_treatment
Pathology and Laboratory Medicine
Vascular Medicine
Biochemistry
Rats
Sprague-Dawley
0302 clinical medicine
Medicine and Health Sciences
Brain Damage
Stroke
Saline
Mammals
Multidisciplinary
Eukaryota
Animal Models
Enzymes
Hemorrhagic Stroke
Dose–response relationship
Neuroprotective Agents
Neurology
Experimental Organism Systems
Osteichthyes
Anesthesia
Vertebrates
Medicine
Administration
Intravenous
Anatomy
medicine.symptom
Research Article
Carps
Histology
Traumatic brain injury
Science
Cerebrovascular Diseases
Hemorrhage
Brain damage
Research and Analysis Methods
Rodents
Lesion
03 medical and health sciences
Signs and Symptoms
Model Organisms
Hematoma
Diagnostic Medicine
medicine
Animals
Collagenases
cardiovascular diseases
Ischemic Stroke
Cerebral Hemorrhage
Intracerebral hemorrhage
Dose-Response Relationship
Drug
business.industry
Organisms
Biology and Life Sciences
Proteins
Recovery of Function
medicine.disease
Rats
Disease Models
Animal
Fish
030104 developmental biology
Amniotes
Enzymology
Animal Studies
Peptides
business
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 11, p e0224870 (2019)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0224870
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: