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 (H 2O 2) is known to be a toxic compound responsible for free-radical-dependent neuronal damage. In recent years, however, the 'bad reputation' of H 2O 2 and other ROS molecules has changed. The aim of this study was to assess the protective role of H 2O 2 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 H 2O 2 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 H 2O 2 (3 mM). The rescuing action of H 2O 2 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 H 2O 2, 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 H 2O 2.
Original language | English |
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Pages (from-to) | 1022-1029 |
Number of pages | 8 |
Journal | British Journal of Pharmacology |
Volume | 153 |
Issue number | 5 |
DOIs | |
Publication status | Published - Mar 2008 |
Keywords
- Electrophysiology
- Hippocampus
- Hydrogen peroxide
- Ischaemia
- Neuroprotection
ASJC Scopus subject areas
- Pharmacology