title: The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis.
abstract: OBJECTIVE
  It has been demonstrated that changes in the normal-appearing white matter (NAWM) in multiple sclerosis precede the appearance of classical lesions. The understanding of NAWM biology in an established disease model might help to clarify why some of them progress to active demyelinating lesions.
  
  
  METHODS
  C57BL6 male mice (19-21 g) were used in this study.
  
  
  METHODS
  Demyelination was induced by feeding mice a diet containing 0.2% cuprizone for up to 5 weeks.
  
  
  METHODS
  Routine stainings (luxol fast blue, and hematoxylin and eosin) and immunohistochemistry were performed to assess myelin status and the inflammatory infiltrate.
  
  
  RESULTS
  We demonstrated that, in the toxic demyelination cuprizone model, the corpus callosum is severely demyelinated after a 5-week cuprizone challenge (acute demyelination) whereas the fimbria of the hippocampus appear normal in routine myelin stainings. Microgliosis but not astrogliosis is evident after acute demyelination in the fimbria. Interestingly, both regions, the fimbria and the corpus callosum, demonstrated early oligodendrocyte apoptosis as well as intense microglia accumulation and activation. However, only the corpus callosum progresses to actively demyelination lesions whereas the fimbria does not.
  
  
  CONCLUSIONS
  The applied model appears suitable for elucidating pathways which promote progression of affected tissue to an active lesion.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany. mkipp@ukaachen.de
authors.forename: M
authors.initials: M
authors.lastname: Kipp
authors.forename: A
authors.initials: A
authors.lastname: Norkus
authors.forename: B
authors.initials: B
authors.lastname: Krauspe
authors.forename: T
authors.initials: T
authors.lastname: Clarner
authors.forename: K
authors.initials: K
authors.lastname: Berger
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: S
authors.initials: S
authors.lastname: Amor
authors.forename: C
authors.initials: C
authors.lastname: Beyer
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003337:Corpus Callosum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone / Q000494:pharmacology* / Q000627:therapeutic use; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D002614:Chelating Agents; D018696:Neuroprotective Agents; D003471:Cuprizone