Argon: Neuroprotection in in vitro models of cerebral ischemia and traumatic brain injury

Philip D Loetscher,Michael Fries,Yu-Mi Ryang,Joachim Weis,Rolf Rossaint,Mark Coburn,Oliver Grottke,Astrid Fahlenkamp,Jan Rossaint

doi:10.1186/cc8214

Abstract

IntroductionRecently, it has been shown in several experimental settings that the noble gases xenon and helium have neuroprotective properties. In this study we tested the hypothesis that the noble gas argon has a neuroprotective potential as well. Since traumatic brain injury and stroke are widespread and generate an enormous economic and social burden, we investigated the possible neuroprotective effect in in vitro models of traumatic brain injury and cerebral ischemia.MethodsOrganotypic hippocampal slice cultures from mice pups were subjected to either oxygen-glucose deprivation or to a focal mechanical trauma and subsequently treated with three different concentrations (25, 50 and 74%) of argon immediately after trauma or with a two-or-three-hour delay. After 72 hours of incubation tissue injury assessment was performed using propidium iodide, a staining agent that becomes fluorescent when it diffuses into damaged cells via disintegrated cell membranes.ResultsWe could show argon's neuroprotective effects at different concentrations when applied directly after oxygen-glucose deprivation or trauma. Even three hours after application, argon was still neuroprotective.ConclusionsArgon showed a neuroprotective effect in both in vitro models of oxygen-glucose deprivation and traumatic brain injury. Our promising results justify further in vivo animal research.

Highlights

It has been shown in several experimental settings that the noble gases xenon and helium have neuroprotective properties
Since traumatic brain injury and stroke are widespread and generate an enormous economic and social burden, we investigated the possible neuroprotective effect in in vitro models of traumatic brain injury and cerebral ischemia
The inserts were placed in tissue culture plates (Sarstedt, Newton, MA, USA) and 0.8 ml growth medium (50% Eagle minimal essential medium with Earle's salts, 25% Hank's balanced salt solution (Sigma-Aldrich, Munich, Germany), 25% heat inactivated horse serum, 2 mM L-glutamine, 5 mg/ml D-glucose, 1% antibiotic/antimycotic solution and 50 mM HEPES buffer solution (Fluka, Buchs, Switzerland), titrated to pH 7.2) was inserted underneath the membrane

Summary

Introduction

It has been shown in several experimental settings that the noble gases xenon and helium have neuroprotective properties. Since traumatic brain injury and stroke are widespread and generate an enormous economic and social burden, we investigated the possible neuroprotective effect in in vitro models of traumatic brain injury and cerebral ischemia. The first biological effects of argon were demonstrated as early as 1939 [1]. Half a century later Soldatov and co-workers [2] were the first to show argon's protective effects under hypoxic conditions. Thereafter, it was reported that argon shields hair cells from ototoxic process [3] and protects cell cultures from ischemia [4]. Xenon's organ protective effects have been investigated in various settings and models, ranging from cell cultures to clinical trials. Xenon has proven to be a safe anaesthetic agent and xenon's organoprotective properties have been demonstrated in many fields [5,6,7,8,9,10,11,12,13,14]

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