Activation of TRESK background potassium channels by cloxyquin exerts protective effects against excitotoxic-induced brain injury and neuroinflammation in neonatal rats

We investigated effects of activation of TRESK channels by selective activator cloxyquin on excitotoxic-induced brain injury and neuroinflammation involving brain mast cells and inflammatory cytokines in neonatal rats. Three different doses of cloxyquin (0.2, 1 and 5 mg/kg) were studied in ibotenate-induced perinatal brain injury (PBI) in P5 rat-pups. Cerebral lesions and mast cells in coronal brain sections were evaluated. Concentrations of activin A, IL-1β, IL-6 and IL-10 in brain homogenates were measured using ELISA. Cloxyquin dose-dependently exerted protective effects against excitotoxic-induced neonatal brain injury and neuroinflammation. TRESK channels may be a promising new target for the treatment of PBIs. Ibotenate leads to white matter cysts and reduced gray and white matter thickness. Additionally, ibotenate induces degranulation of brain mast cells and increases the concentrations of pro-inflammatory cytokines IL-1β and IL-6 in the brain tissue while it decreases IL-10 level, thus leading to the neuroinflammation. However, cloxyquin dose-dependently prevents excitotoxic-induced neonatal brain injury and the neuroinflammation. [Display omitted] •Ibotenate led to excitotoxic-induced brain injury.•Ibotenate induced massive degranulation of brain mast cells and increased their number.•Ibotenate increased concentrations of activin A, IL-1β and IL-6 in brain tissue.•Cloxyquin dose-dependently ameliorated ibotenate-induced impairments in the cerebral gray and white matter.•Cloxyquin dose-dependently suppressed brain mast cells, and stimulated-levels of activin A, IL-1β and IL-6 in brain tissue.