title: Cerebral oedema is not responsible for motor or cognitive deficits in rats with hepatic encephalopathy.
abstract: OBJECTIVE
  Low-grade cytotoxic oedema is considered a main contributor to the neurological (motor and cognitive) alterations in patients with hepatic encephalopathy (HE). This assumption is mainly based on studies with cultured astrocytes treated with very large ammonia concentrations or with animal models of acute liver failure with strong HE. However, the possible contribution of cerebral oedema (vasogenic or cytotoxic) to cognitive or motor alterations in chronic mild HE has not been demonstrated. The aim of this work was to assess whether cerebral oedema contributes to cognitive and/or motor alterations in rats with chronic mild HE.
  
  
  METHODS
  Motor activity and coordination and different types of learning and memory were assessed in rats with porta-caval shunts (PCS). Brain oedema was assessed by gravimetry in cerebellum and cortex and apparent diffusion coefficient (ADC) by magnetic resonance in 16 areas.
  
  
  RESULTS
  Four weeks after surgery, PCS rats show reduced motor activity and coordination, impaired ability to learn a conditional discrimination task in the Y maze and reduced spatial memory in the Morris water maze. PCS rats did not show increased brain water content at 4 or 10 weeks or changes in ADC at 4 weeks. At 10 weeks, increased ADC in some areas is compatible with vasogenic but not cytotoxic oedema.
  
  
  CONCLUSIONS
  Cerebral oedema is not involved in motor and cognitive alterations in rats (and likely in humans) with mild HE. Proper understanding of the mechanisms responsible for the neurological alterations in HE is necessary to design efficient treatments.
authors.affiliation: Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
authors.forename: Ana
authors.initials: A
authors.lastname: Agustí
authors.forename: Regina
authors.initials: R
authors.lastname: Rodrigo
authors.forename: Vicente
authors.initials: V
authors.lastname: Hernández-Rabaza
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Larrubia
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cerdán
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000175:diagnosis*; D002531:Cerebellum / Q000000981:diagnostic imaging*; D003071:Cognition; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D008568:Memory; D009043:Motor Activity; D011167:Portacaval Shunt, Surgical; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar
keywords: cytotoxic oedema; inflammation; learning; memory; minimal hepatic encephalopathy; motor function