Free radical formation and mitochondrial damage in epilepsy – a reperfusion injury

Abstract

Event Abstract Back to Event Free radical formation and mitochondrial damage in epilepsy – a reperfusion injury Richárd Kovács1*, Christine Huchzermeyer1, Ismini Papageorgiu1, Oliver Kann1 and Uwe Heinemann1 1 Charite-Universitatsmedizin Berlin, Germany Several lines of evidence indicate that reactive oxygen species (ROS) formation is strongly enhanced during epileptic activity leading to mitochondrial dysfunction, energy failure and neuronal cell death. Nevertheless, the sources and targets of ROS have not been identified yet. Here we studied kinetics and spatial pattern of ROS formation in an in vitro model of epilepsy by using electrophysiology, oxygen electrode recordings, microfluorimetry and confocal microscopy. Seizure-like events (SLEs) were associated with biphasic transients of NAD(P)H fluorescence, indicating initial oxidation (dip) followed by a lasting reduction (overshoot) of NAD(P)H. Tissue pO2 decreased by ~107 mmHg during SLEs, but it remained clearly hyperoxic. NAD(P)H dip and overshoot were significantly faster than the peak and recovery of pO2, respectively. Decreasing electron transport chain activity in the presence of high O2 and increased NAD(P)H/NAD(P)+ ratio was associated with an increase in ROS formation, as revealed by the oxidation of mitochondrialy targeted hydroethidine (MitoSox). Co-localisation of MitoSox with mitochondrial as well as with neuronal and astrocytic markers indicated ROS formation in neuronal mitochondria. Mitochondria showed considerable heterogeneity in shape, motility and MitoSox fluorescence. Mitochondria with high levels of ROS were less motile and occasionally underwent thread to grain transition. Remarkably, massive ROS formation was observed in mitochondria of capillary pericytes, leading to contraction of capillaries at late stages of the experimental status epilepticus. Thus we concluded that ROS formation occurs in neurons when electron transport chain activity decreases in the presence of high levels of reducing equivalents and O2. Such conditions may occur in vivo during seizure associated increases in blood flow, whereas ROS dependent capillary constriction might be responsible for disturbances of neurovascular coupling during lasting status epilepticus. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Disorders of the nervous system Citation: Kovács R, Huchzermeyer C, Papageorgiu I, Kann O and Heinemann U (2010). Free radical formation and mitochondrial damage in epilepsy – a reperfusion injury. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00039 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Apr 2010; Published Online: 20 Apr 2010. * Correspondence: Richárd Kovács, Charite-Universitatsmedizin Berlin, Berlin, Germany, richard.kovacs@charite.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Richárd Kovács Christine Huchzermeyer Ismini Papageorgiu Oliver Kann Uwe Heinemann Google Richárd Kovács Christine Huchzermeyer Ismini Papageorgiu Oliver Kann Uwe Heinemann Google Scholar Richárd Kovács Christine Huchzermeyer Ismini Papageorgiu Oliver Kann Uwe Heinemann PubMed Richárd Kovács Christine Huchzermeyer Ismini Papageorgiu Oliver Kann Uwe Heinemann Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.