Chronic hydrocephalus in rats and humans: white matter loss and behavior changes

Ann Neurol. 2003 Mar;53(3):337-46. doi: 10.1002/ana.10453.


Chronic hydrocephalus that begins in childhood and progresses only very gradually is sometimes called "arrested" hydrocephalus. Data suggest that this state eventually can become symptomatic and may be treatable by shunting. However, the pathological substrate of the disorder is not entirely understood. We studied chronic hydrocephalus in rats, 9 months after induction by kaolin injection into the cisterna magna, and in humans. In both circumstances, destruction of periventricular white matter structures was worst in those with the largest ventricles. Structures damaged include the corpus callosum, corticospinal tract, and fimbria/fornix projections from the hippocampus. Myelin turnover was increased. These changes were associated with deficits of motor and cognitive function. The cerebral cortex was largely spared. There appears to be a threshold of ventricle size beyond which functional changes manifest, but this undoubtedly is modified by factors such as age of onset and rate of enlargement. These data support the need for persistent follow-up of patients with chronic, apparently stable hydrocephalus. A slight increase in size of already enlarged ventricles might cause significant axonal damage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Brain / metabolism
  • Brain / pathology*
  • Cerebral Ventricles / metabolism
  • Cerebral Ventricles / pathology*
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology*
  • Humans
  • Hydrocephalus / chemically induced
  • Hydrocephalus / metabolism
  • Hydrocephalus / pathology*
  • Infant
  • Kaolin / toxicity
  • Male
  • Middle Aged
  • Motor Skills Disorders / metabolism
  • Motor Skills Disorders / pathology*
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Statistics, Nonparametric


  • Kaolin