Poly-arginine (e.g. (Arg)9) with cell-penetrating properties are neuroprotective. (Arg)9 provides significant neuroprotection in a dose–response manner following glutamic acid exposure with IC50 of 0.78 μM. Following kainic acid exposure, (Arg)9 is neuroprotective, but less effective than in the glutamic acid model with IC50 of 0.81 μM. (Arg)9 also shows neuroprotection following in vitro ischemia with IC50 of 6 μM[1].

In rat stroke models, (Arg)9) (D-isoform) is neuroprotective. (Arg)9) is highly neuroprotective, with efficacy increasing with increasing arginine content, has the capacity to reduce glutamic acid-induced neuronal calcium influx and requires heparan sulfate preotoglycan-mediated endocytosis to induce a neuroprotective effect[2]. (Arg) 9) (D-isoform) was administered intravenously at a dose of 1000 nmol/kg 30 minutes after permanent middle cerebral artery occlusion (MCAO) [3].