Effect of Polyarginine Peptide R18D Following a Traumatic Brain Injury in Sprague-Dawley Rats

Li Shan Chiu; Ryan S Anderton; Vince W Clark; Jane L Cross; Neville W Knuckey; Bruno P Meloni

doi:10.1016/j.curtheres.2020.100584

Effect of Polyarginine Peptide R18D Following a Traumatic Brain Injury in Sprague-Dawley Rats

Curr Ther Res Clin Exp. 2020 Mar 19:92:100584. doi: 10.1016/j.curtheres.2020.100584. eCollection 2020.

Authors

Li Shan Chiu^{1

2}, Ryan S Anderton^{1

2

3

4}, Vince W Clark^{1

2

5}, Jane L Cross^{1

2

5}, Neville W Knuckey^{1

2

5}, Bruno P Meloni^{1

2

5}

Affiliations

¹ Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
² Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Western Australia, Australia.
³ School of Heath Sciences, The University Notre Dame Australia, Fremantle, Western Australia, Australia.
⁴ Institute for Health Research, The University Notre Dame Australia, Fremantle, Western Australia, Australia.
⁵ Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, Western Australia, Australia.

Abstract

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.

Results: At postinjury day 3, treatment with R18D at the high dose significantly reduced axonal injury (P = 0.044), whereas the low-dose treatment of R18D showed a trend for reduced axonal injury. Following assessment in the Barnes maze, both doses of R18D treatment appeared to improve learning and memory recovery compared with vehicle treatment at postinjury days 1 and 3, albeit not to a statistically significant level. Rotarod assessment of vestibulomotor recovery did not differ between R18D and the vehicle treatment groups.

Conclusions: R18D modestly decreased axonal injury only at the highest dose used but had no significant effect on functional recovery. These findings warrant further studies with additional doses to better understand peptide pharmacodynamics and provide information to guide optimal dosing.

Keywords: Cationic arginine-rich peptides; Diffuse axonal injury; Neuroprotection; R18D; TBI.