We examined the neuroprotective efficacy of the poly-arginine peptide R18 and its D-enantiomer R18D in a perinatal hypoxic-ischaemic (HI) model in P7 Sprague-Dawley rats. R18 and R18D peptides were administered intraperitoneally at doses of 30, 100, 300 or 1000 nmol/kg immediately after HI (8% O/92%N for 2.5 h). The previously characterised neuroprotective JNKI-1-TATD peptide at a dose of 1000 nmol/kg was used as a control. Infarct volume and behavioural outcomes were measured 48 h after HI. For the R18 and R18D doses examined, total infarct volume was reduced by 25.93% to 43.80% (P = 0.038 to < 0.001). By comparison, the JNKI-1-TATD reduced lesion volume by 25.27% (P = 0.073). Moreover, R18 and R18D treatment resulted in significant improvements in behavioural outcomes, while with JNKI-1-TATD there was a trend towards improvement. As an insight into the likely mechanism underlying the effects of R18, R18D and JNKI-1-TATD, the peptides were added to cortical neuronal cultures exposed to glutamic acid excitotoxicity, resulting in up to 89, 100 and 71% neuroprotection, respectively, and a dose dependent inhibition of neuronal calcium influx. The study further confirms the neuroprotective properties of poly-arginine peptides, and suggests a potential therapeutic role for R18 and R18D in the treatment of HIE.
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http://dx.doi.org/10.1186/s13041-018-0352-0 | DOI Listing |
Brain Behav
January 2023
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Background: Disparities exist regarding an efficient treatment for stroke. Polyarginines have shown promising neuroprotective properties based on available published studies. Thus, the present study aims to systemically review and analyze existing evidence regarding polyarginine's administration efficacy in animal stroke models.
View Article and Find Full Text PDFBiochem Biophys Rep
September 2022
Perron Institute for Neurological and Translational Sciences, First Floor, RR-Block, QEII Medical Centre, Nedlands, Western Australia, Australia.
Our laboratory focuses on the development of novel neuroprotective cationic peptides, such poly-arginine-18 (R18: 18-mer of l-arginine; net charge +18) and its d-enantiomer R18D in stroke and other brain injuries. In the clinical development of R18/R18D, their cationic property raises potential safety concerns on their non-specific effects to induce mast cell degranulation and hemolysis. To address this, we first utilised primary human cultured mast cells (HCMCs) to examine anaphylactoid effects.
View Article and Find Full Text PDFJ Thromb Thrombolysis
July 2022
Perron Institute for Neurological and Translational Sciences, QEII Medical Centre, RR Block, 8 Verdun St, Nedlands, WA, 6009, Australia.
The poly-arginine peptides R18D and R18 represent novel potential neuroprotective treatments for acute ischaemic stroke. Here we examined whether R18D and R18 had any significant effects on the thrombolytic activity of alteplase (tPA) and tenecteplase (TNK) on clots formed from whole blood in an in vitro thrombolysis plate assay. R18D and R18 were examined at concentrations of 0.
View Article and Find Full Text PDFNeurochem Res
May 2021
Perron Institute for Neurological and Translational Sciences, QEII Medical Centre, Nedlands, WA, 6009, Australia.
Poly-arginine peptides R18 and R18D have previously been demonstrated to be neuroprotective in ischaemic stroke models. Here we examined the proteolytic stability and efficacy of R18 and R18D in reducing infarct core growth and preserving the ischaemic penumbra following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. R18 (300 or 1000 nmol/kg), R18D (300 nmol/kg) or saline were administered intravenously 10 min after MCAO induced using a filament.
View Article and Find Full Text PDFCurr Ther Res Clin Exp
March 2020
Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
Background: Despite extensive studies, there are still no clinically available neuroprotective treatments for traumatic brain injury.
Objectives: In previous studies we demonstrated beneficial treatment effects of polyarginine peptides R18 (18-mer of arginine; 300 nmol/kg) and R18D (18-mer of D-arginine; 1000 nmol/kg) in a rat model of impact-acceleration closed-head injury.
Methods: We examined the efficacy of R18D when intravenously administered at a low (100 nmol/kg) and high (1000 nmol/kg) dose, 30 minutes after a closed-head injury in male Sprague-Dawley rats.
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