Cationic arginine-rich peptides (CARPs) such as the poly-arginine R18 and R18D peptides have demonstrated neuroprotective efficacy in in vitro neuronal excitotoxic injury and in vivo rat models of stroke. These peptides have also demonstrated significantly reduced axonal injury and positive trends for functional recovery in a rat model of traumatic brain injury (TBI). Currently, there are no neuroprotective pharmacological treatments for TBI.  Since poly-arginine peptides have demonstrated neuroprotective potential, both R18 and R18D were further characterised in a rat model of TBI. Using a weight-drop impact-acceleration apparatus, a closed-head TBI was induced in male rats.  A dose-response study using R18D (100, 300, 1000 nmol/kg) administered intravenously at 30-min post-injury was conducted in Sprague-Dawley rats. A second study in Long-Evans rats examined R18 and R18D at a dose of 1000 nmol/kg administered intravenously at 30-min post-injury. In the Sprague-Dawley rat, doses of R18D at 100 and 1000 nmol/kg significantly reduced the extent of axonal injury in the corpus callosum, and demonstrated significant improvement in learning and memory outcome.  In the Long-Evans rat, both R18 and R18D significantly reduced astrocytic activation, and reduced IL-6 levels in the brain following injury. R18D was particularly effective at improving sensorimotor function and generally produced more favourable functional outcomes than R18. Poly-arginine peptides have neuroprotective effects following TBI and warrant continued investigation as a novel therapeutic for TBI.

Cationic Arginine-Rich Peptides Have Therapeutic Potential Following Traumatic Brain Injury in the Rat