Poly-arginine Peptide R18D Reduces Neuroinflammation and Functional Deficits Following Traumatic Brain Injury in the Long-Evans Rat

  • Li Shan ChiuEmail author
  • Ryan S. Anderton
  • Jane L. Cross
  • Vince W. Clark
  • Neville W. Knuckey
  • Bruno P. Meloni


We have previously demonstrated that the poly-arginine peptide R18 can improve histological and functional outcomes following traumatic brain injury (TBI) in the Sprague–Dawley rat. Since D-enantiomer peptides are often exploited in pharmacology for their increased stability and potency, the present study compared the effects of R18 and its D-enantiomer, R18D, following TBI in the Long-Evans rat. Following a closed-head impact delivered via a weight-drop apparatus, peptide was administered at a dose of 1000 nmol/kg at 30 min after TBI. Treatment with R18D, but not R18 resulted in significant reductions in sensorimotor (p = 0.026) and vestibulomotor (p = 0.049) deficits as measured by the adhesive tape removal and rotarod tests. Furthermore, treatment with R18 and R18D resulted in a significant reduction in brain protein levels of the astrocytic marker, glial fibrillary acidic protein (p = 0.019 and 0.048, respectively). These results further highlight the beneficial effects of poly-arginine peptides in TBI, however additional studies are required to confirm these positive effects.


Neuroprotection Arginine-rich Peptide TBI Inflammation 



This study was supported by grants from the Neurotrauma Research Program of Western Australia, Insurance Commission of Western Australia, and Brain Foundation (Australia). Financial support was also provided by the Perron Institute for Neurological and Translational Science and the Department of Neurosurgery at Sir Charles Gairdner Hospital. We thank Jim Litis for providing a student PhD scholarship for Li Shan Chiu. The authors would also like to thank Professor Frank Mastaglia for his assistance in the preparation of this manuscript.

Compliance with Ethical Standards

Conflict of interest

Bruno P. Meloni and Neville W. Knuckey are the holders of several patents regarding the use of arginine-rich peptides as neuroprotective treatments. The other authors declare no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Perron Institute for Neurological and Translational ScienceQEII Medical CentreNedlandsAustralia
  2. 2.Centre for Neuromuscular and Neurological DisordersThe University of Western AustraliaNedlandsAustralia
  3. 3.Department of Neurosurgery, Sir Charles Gairdner HospitalQEII Medical CentreNedlandsAustralia
  4. 4.School of Heath SciencesThe University Notre Dame AustraliaFremantleAustralia
  5. 5.Institute for Health ResearchThe University Notre Dame AustraliaFremantleAustralia

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