Research Paper
Subject Category: Neuropharmacology
British Journal of Pharmacology (2008) 153, 1022–1029; doi:10.1038/sj.bjp.0707587; published online 28 January 2008
Neuroprotective effect of hydrogen peroxide on an in vitro model of brain ischaemia
R Nisticò1,2, S Piccirilli1,3, M L Cucchiaroni1, M Armogida1, E Guatteo1, C Giampà1, F R Fusco1, G Bernardi1,4, G Nisticò3,5 and N B Mercuri1,5
- 1C.E.R.C.—S Lucia Foundation IRCCS, Rome, Italy
- 2Department of Pharmacobiology, University of Calabria, Rende, Italy
- 3'Mondino-Tor Vergata' Center for Neuropharmacology, University of Rome 'Tor Vergata', Rome, Italy
- 4Neurological Clinic, University of Rome 'Tor Vergata', Rome, Italy
- 5Centre of Pharmaceutical Biotechnology, University of Rome 'Tor Vergata', Rome, Italy
Correspondence: Dr R Nisticò Department of Pharmacobiology, University of Calabria, Via Pietro Bucci, 87036 Rende (CS), Italy. E-mail: robert.nistico@gmail.com
Received 24 July 2007; Revised 17 September 2007; Accepted 17 October 2007; Published online 28 January 2008.
Abstract
Background and purpose:
Reactive oxygen species (ROS) have been postulated to play a crucial role in the pathogenesis of ischaemia-reperfusion injury. Among these, hydrogen peroxide (H2O2) is known to be a toxic compound responsible for free-radical-dependent neuronal damage. In recent years, however, the 'bad reputation' of H2O2 and other ROS molecules has changed. The aim of this study was to assess the protective role of H2O2 and modification in its endogenous production on the electrophysiological and morphological changes induced by oxygen/glucose deprivation (OGD) on CA1 hippocampal neurons.
Experimental approach:
Neuroprotective effects of exogenous and endogenous H2O2 were determined using extracellular electrophysiological recordings of field excitatory post synaptic potentials (fEPSPs) and morphological studies in a hippocampal slice preparation. In vitro OGD was delivered by switching to an artificial cerebrospinal fluid solution with no glucose and with oxygen replaced by nitrogen.
Key results:
Neuroprotection against in vitro OGD was observed in slices treated with H2O2 (3 mM). The rescuing action of H2O2 was mediated by catalase as pre-treatment with the catalase inhibitor 3-amino-1,2,4-triazole blocked this effect. More interestingly, we showed that an increase of the endogenous levels of H2O2, due to a combination of an inhibitor of the glutathione peroxidase enzyme and addition of Cu,Zn-superoxide dismutase in the tissue bath, prevented the OGD-induced irreversible depression of fEPSPs.
Conclusions and implications:
Taken together, our results suggest new possible strategies to lessen the damage produced by a transient brain ischaemia by increasing the endogenous tissue level of H2O2.
Keywords:
hydrogen peroxide, ischaemia, electrophysiology, hippocampus, neuroprotection
Abbreviations:
ACSF, artificial cerebral spinal fluid; 3-AT, 3-amino-1,2,4-triazole; fEPSP, field excitatory postsynaptic potentials; GD, glucose deprivation; GPXs, glutathione peroxidases; MPS, mercaptosuccinate; O2-, superoxide anion; OGD, oxygen/glucose deprivation; OH-, hydroxyl radical; ROS, reactive oxygen species; SOD, superoxide dismutase
