The Oligopeptides, Homologous of ACTH15-18 Sequence: Neurotrophic and Anti-inflammatory Activity on the Model of Cerebral Ischemia in Rats

Abstract

Abstract: The series of tetrapeptides, homologues of ACTH15-18 sequence that contain D-form of lysine and arginine have been synthesized at the State Research Institute of Highly Pure Biopreparations (Saint-Petersburg, Russian Federation). Previous research allowed to reveal their neuroprotectivе, anti-hypoxic and favorable psychotropic properties and capability to stimulate blood supply to the injured brain. The influence of neuropeptide on rats survival, neurological deficit (ND), nerve growth factor (NGF) expression, tumor necrosis factor α (TNF-α), interleukine-1 beta (IL-1β) and interleukine-4 (IL-4) levels in rats brain tissue was studied on the irreversible bilateral carotid occlusion model. Neuroprotectivе properties of the neuropeptides KK-1 and KK-5 namely increase in rats with acute ischemic stroke (AIS) survival rate up to 75% and 80%, respectively, were shown. Neuropeptides decreased ND 1.7 times compared with the untreated group (UG). Neuroprotectivе effect of the neuropeptides is manifested by their ability to decrease the level of NGF compensatory overexpression, proinflammatory and anti-inflammatory cytokines such as TNF-α, IL-1β, IL-4. It has been established that the mechanism of the tetrapeptides KK-1 and KK-5 neuroprotectivе activity is connected with their neurotrophic and anti-inflammatory action.