title: The protective role of catalase against cerebral ischemia in vitro and in vivo.
abstract: The present study aims to assess the protective role of the antioxidant enzyme catalase (CAT) with relation to hydrogen peroxide (H(2)O(2)) degradation in oxygen plus water on electrophysiological and fluorescence changes induced by in vitro ischemia and on brain damage produced by transient in vivo ischemia. Neuroprotective effects of CAT were determined by means of electrophysiological recordings and confocal fluorescence microscopy in the hippocampal slice preparation. Ischemia was simulated in vitro by oxygen/glucose deprivation (OGD). In vivo ischemia was produced by transient middle cerebral artery occlusion (MCAo). A protection of the rat CA1 field excitatory postsynaptic potential (fEPSP) loss caused by a prolonged OGD (40 min) was observed after exogenous CAT (500 U/mL) bath-applied before a combined exposure to OGD and H(2)O(2) (3 mM). Of note, neither H(2)O(2) nor exogenous CAT alone had a protective action when OGD lasted for 40 min. The CAT-induced neuroprotection was confirmed in a transgenic mouse model over-expressing human CAT [Tg(CAT)]. In the presence of H(2)O(2), the hippocampus of Tg(CAT) showed an increased resistance against OGD compared to that of wild-type (WT) animals. Moreover, CAT treatment reduced for about 50 min fEPSP depression evoked by repeated applications of H(2)O(2) in normoxia. A lower sensitivity to H(2)O(2)-induced depression of fEPSPs was also indicated by the rightward shift of concentration-response curve in Tg(CAT) compared to WT mice. Noteworthy, Tg(CAT) mice had a reduced infarct size after MCAo. Our data suggest new strategies to reduce neuronal damage produced by transient brain ischemia through the manipulation of CAT enzyme.
authors: Laboratory of Experimental Neurology, Fondazione Santa Lucia IRCCS, Rome.
authors: M
authors: M
authors: Armogida
authors: A
authors: A
authors: Spalloni
authors: D
authors: D
authors: Amantea
authors: M
authors: M
authors: Nutini
authors: F
authors: F
authors: Petrelli
authors: P
authors: P
authors: Longone
authors: G
authors: G
authors: Bagetta
authors: R
authors: R
authors: Nisticò
authors: Nicola Biagio
authors: NB
authors: Mercuri
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000473:pathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D006861:Hydrogen Peroxide / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D016877:Oxidants / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D016877:Oxidants; D013481:Superoxides; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose