Chitosan nanoparticles release nimodipine in response to tissue acidosis to attenuate spreading depolarization evoked during forebrain ischemia.

Chitosan nanoparticles release nimodipine in response to tissue acidosis to attenuate spreading depolarization evoked during forebrain ischemia. Neuropharmacology. 2019 Nov 09;:107850 Authors: Tóth OM, Menyhárt Á, Varga VÉ, Hantosi D, Ivánkovits-Kiss O, Varga DP, Szabó Í, Janovák L, Dékány I, Farkas E, Bari F Abstract Stroke is an important cause of mortality and disability. Treatment options are limited, therefore the progress in this regard is urgently needed. Nimodipine, an L-type voltage-gated calcium channel antagonist dilates cerebral arterioles, but its systemic administration may cause potential side effects. We have previously constructed chitosan nanoparticles as drug carriers, which release nimodipine in response to decreasing pH typical of cerebral ischemia. Here we have set out to evaluate this nanomedical approach to deliver nimodipine selectively to acidic ischemic brain tissue. After washing a nanoparticle suspension with or without nimodipine (100 μM) on the exposed brain surface of anesthetized rats (n = 18), both common carotid arteries were occluded to create forebrain ischemia. Spreading depolarizations (SDs) were elicited by 1M KCl to deepen the ischemic insults. Local field potential, cerebral blood flow (CBF) and tissue pH were recorded from the cerebral cortex. Microglial activation and neuronal survival were evaluated in brain sections by immunocytochemistry. Ischemia-induced tissue acidosis...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research