Neuroanatomical, sensorimotor and cognitive deficits in adult rats with white matter injury following prenatal ischemia

Brain Pathol. 2012 Jan;22(1):1-16. doi: 10.1111/j.1750-3639.2011.00504.x. Epub 2011 Aug 16.

Abstract

Perinatal brain injury including white matter damage (WMD) is highly related to sensory, motor or cognitive impairments in humans born prematurely. Our aim was to examine the neuroanatomical, functional and behavioral changes in adult rats that experienced prenatal ischemia (PI), thereby inducing WMD. PI was induced by unilateral uterine artery ligation at E17 in pregnant rats. We assessed performances in gait, cognitive abilities and topographical organization of maps, and neuronal and glial density in primary motor and somatosensory cortices, the hippocampus and prefrontal cortex, as well as axonal degeneration and astrogliosis in white matter tracts. We found WMD in corpus callosum and brainstem, and associated with the hippocampus and somatosensory cortex, but not the motor cortex after PI. PI rats exhibited mild locomotor impairments associated with minor signs of spasticity. Motor map organization and neuronal density were normal in PI rats, contrasting with major somatosensory map disorganization, reduced neuronal density, and a marked reduction of inhibitory interneurons. PI rats exhibited spontaneous hyperactivity in open-field test and short-term memory deficits associated with abnormal neuronal density in related brain areas. Thus, this model reproduces in adult PI rats the main deficits observed in infants with a perinatal history of hypoxia-ischemia and WMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavioral Symptoms / pathology
  • Behavioral Symptoms / physiopathology
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology*
  • Cognition Disorders / physiopathology*
  • Disease Models, Animal
  • Female
  • Hypoxia-Ischemia, Brain / pathology*
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Male
  • Nerve Fibers, Myelinated / pathology
  • Nerve Fibers, Myelinated / physiology
  • Neurons / pathology*
  • Neurons / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology*
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Sprague-Dawley