title: General Anesthesia Causes Long-term Impairment of Mitochondrial Morphogenesis and Synaptic Transmission in Developing Rat Brain.
abstract: BACKGROUND
  Clinically used general anesthetics, alone or in combination, are damaging to the developing mammalian brain. In addition to causing widespread apoptotic neurodegeneration in vulnerable brain regions, exposure to general anesthesia at the peak of synaptogenesis causes learning and memory deficiencies later in life. In vivo rodent studies have suggested that activation of the intrinsic (mitochondria-dependent) apoptotic pathway is the earliest warning sign of neuronal damage, suggesting that a disturbance in mitochondrial integrity and function could be the earliest triggering events.
  
  
  METHODS
  Because proper and timely mitochondrial morphogenesis is critical for brain development, the authors examined the long-term effects of a commonly used anesthesia combination (isoflurane, nitrous oxide, and midazolam) on the regional distribution, ultrastructural properties, and electron transport chain function of mitochondria, as well as synaptic neurotransmission, in the subiculum of rat pups.
  
  
  RESULTS
  This anesthesia, administered at the peak of synaptogenesis, causes protracted injury to mitochondria, including significant enlargement of mitochondria (more than 30%, P < 0.05), impairment of their structural integrity, an approximately 28% increase in their complex IV activity (P < 0.05), and a twofold decrease in their regional distribution in presynaptic neuronal profiles (P < 0.05), where their presence is important for the normal development and functioning of synapses. Consequently, the authors showed that impaired mitochondrial morphogenesis is accompanied by heightened autophagic activity, decrease in mitochondrial density (approximately 27%, P < 0.05), and long-lasting disturbances in inhibitory synaptic neurotransmission. The interrelation of these phenomena remains to be established.
  
  
  CONCLUSIONS
  Developing mitochondria are exquisitely vulnerable to general anesthesia and may be important early target of anesthesia-induced developmental neurodegeneration.
authors: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
authors: Victoria
authors: V
authors: Sanchez
authors: Shawn D
authors: SD
authors: Feinstein
authors: Nadia
authors: N
authors: Lunardi
authors: Pavle M
authors: PM
authors: Joksovic
authors: Annalisa
authors: A
authors: Boscolo
authors: Slobodan M
authors: SM
authors: Todorovic
authors: Vesna
authors: V
authors: Jevtovic-Todorovic
mesh_terms: D000768:Anesthesia, General / Q000009:adverse effects; D018681:Anesthetics, General / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D009024:Morphogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018681:Anesthetics, General