title: Mild hypothermia prevents brain edema and attenuates up-regulation of the astrocytic benzodiazepine receptor in experimental acute liver failure.
abstract: OBJECTIVE
  Mild hypothermia has proven useful in the clinical management of patients with acute liver failure. Acute liver failure in experimental animals results in alterations in the expression of genes coding for astrocytic proteins including the "peripheral-type" (astrocytic) benzodiazepine receptor (PTBR), a mitochondrial complex associated with neurosteroid synthesis. To gain further insight into the mechanisms whereby hypothermia attenuates the neurological complications of acute liver failure, we investigated PTBR expression in the brains of hepatic devascularized rats under normothermic (37 degrees C) and hypothermic (35 degrees C) conditions.
  
  
  METHODS
  PTBR mRNA was measured using semi-quantitative RT-PCR in cerebral cortical extracts and densities of PTBR sites were measured by quantitative receptor autoradiagraphy. Brain pregnenolone content was measured by radioimmunoassay.
  
  
  RESULTS
  At coma stages of encephalopathy, animals with acute liver failure manifested a significant increase of PTBR mRNA levels. Brain pregnenolone content and [(3)H]PK 11195 binding site densities were concomitantly increased. Mild hypothermia prevented brain edema and significantly attenuated the increased receptor expression and pregnenolone content.
  
  
  CONCLUSIONS
  These findings suggest that an attenuation of PTBR up-regulation resulting in the prevention of increased brain neurosteroid content represents one of the mechanisms by which mild hypothermia exerts its protective effects in ALF.
authors.affiliation: Neuroscience Research Unit, C.H.U.M. (Hôpital Saint-Luc), 1058 St-Denis, Montreal, Que., Canada.
authors.forename: Mireille
authors.initials: M
authors.lastname: Bélanger
authors.forename: Paul
authors.initials: P
authors.lastname: Desjardins
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chatauret
authors.forename: Christopher
authors.initials: C
authors.lastname: Rose
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007036:Hypothermia, Induced; D017114:Liver Failure, Acute / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D011963:Receptors, GABA-A; D011284:Pregnenolone