title: Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism.
abstract: BACKGROUND
  Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear.
  
  
  METHODS
  The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo.
  
  
  RESULTS
  When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats.
  
  
  CONCLUSIONS
  These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.
authors.affiliation: Dipartimento di Area Critica Medico Chirurgica, Sezione di Anestesiologia e Terapia Intensiva, Università di Firenze, Italy. chiara.adembri@unifi.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Adembri
authors.forename: Luna
authors.initials: L
authors.lastname: Venturi
authors.forename: Alessia
authors.initials: A
authors.lastname: Tani
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
authors.forename: Elena
authors.initials: E
authors.lastname: Gramigni
authors.forename: Andrea
authors.initials: A
authors.lastname: Cozzi
authors.forename: Tristano
authors.initials: T
authors.lastname: Pancani
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: De Gaudio
authors.forename: Domenico E
authors.initials: DE
authors.lastname: Pellegrini-Giampietro
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology* / Q000523:psychology; D002118:Calcium / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D000860:Hypoxia / Q000473:pathology; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects*; D018696:Neuroprotective Agents; D010539:Permeability / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D018686:Anesthetics, Intravenous; D018696:Neuroprotective Agents; D005947:Glucose; D002118:Calcium; D015742:Propofol