title: A Novel Experimental Animal Model of Adult Chronic Hydrocephalus.
abstract: BACKGROUND
  The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown.
  
  
  OBJECTIVE
  To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus.
  
  
  METHODS
  Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed.
  
  
  RESULTS
  Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement.
  
  
  CONCLUSIONS
  Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus.
  
  
  BACKGROUND
  NPH, normal pressure hydrocephalus.
authors.affiliation: *Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland; ‡Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland; §F. M. Kirby Research Center for Functional Brain Imaging at the Kennedy Krieger Institute, School of Medicine, Johns Hopkins University, Baltimore, Maryland; ¶Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, Maryland; ‖Department of Biomedical Engeniering, Johns Hopkins University, Baltimore, Maryland; #Department of Pathology, Division of Neurophatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; **Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; ‡‡Laboratory of Neuroscience, Facultad de Psicologia, University of Colima, Colima, Mexico; §§Department of Neurosurgery, School of Medicine in St. Louis, Washington University, St. Louis, Missouri; ¶¶Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland; ‖‖Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Jusué-Torres
authors.forename: Lee H
authors.initials: LH
authors.lastname: Jeon
authors.forename: Eric W
authors.initials: EW
authors.lastname: Sankey
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lu
authors.forename: Tito
authors.initials: T
authors.lastname: Vivas-Buitrago
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Crawford
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
authors.forename: Jiadi
authors.initials: J
authors.lastname: Xu
authors.forename: Ari
authors.initials: A
authors.lastname: Blitz
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Herzka
authors.forename: Barbara
authors.initials: B
authors.lastname: Crain
authors.forename: Alicia
authors.initials: A
authors.lastname: Hulbert
authors.forename: Hugo
authors.initials: H
authors.lastname: Guerrero-Cazares
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalez-Perez
authors.forename: James P
authors.initials: JP
authors.lastname: McAllister
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
authors.forename: Daniele
authors.initials: D
authors.lastname: Rigamonti
mesh_terms: D000818:Animals; D003071:Cognition; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005684:Gait; D006849:Hydrocephalus / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006850:Hydrocephalus, Normal Pressure / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation; D007616:Kaolin / Q000633:toxicity; D008124:Locomotion; D008279:Magnetic Resonance Imaging; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013346:Subarachnoid Space / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D007616:Kaolin