Evaluation of neuroprotective effects of insulin on immuno-inflammatory and systemic disorders induced by kaliotoxin, a Kv1.3 channel blocker.

Abstract

Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid residues. It is purified from Androctonus australis scorpion venom. The binding of KTX2 to its targets is able to alter the neuronal excitability leading to neurological disorders, accompanied by an inflammatory response. In brain, activation of insulin receptor signaling pathway by insulin induces current suppression and concomitant tyrosine phosphorylation of Kv1.3 channel. The aim of this study is to evaluate the effect of insulin injected by i.c.v. route on the neuro-pathophysiological and systemic disorders induced by KTX2. Tissue damage, inflammatory response and oxidative stress biomarkers were assessed in NMRI mice at 24h after co-injection of KTX2 and insulin by intracerebroventricular route. Obtained results revealed that the central administration of insulin prevents cerebral cortex injury, brain edema and blood-brain barrier alteration induced by KTX2, these are accompanied by significant decrease of systemic disorders including serum cytokines, inflammatory and oxidative stress markers and tissue damage. These results indicate that insulin is able to reduce neuro-immunological effects and systemic disorders induced by KTX2. The neuroprotective effect of insulin may be due to its crucial role in the regulation of inflammation response and its properties to modulate the activity of Kv1.3 channels in brain.