Long-term deficits following cerebral hypoxia-ischemia in four-week-old rats: correspondence between behavioral, histological, and magnetic resonance imaging assessments

Exp Neurol. 2001 Feb;167(2):272-81. doi: 10.1006/exnr.2000.7565.

Abstract

We examined whether following a hypoxic-ischemic insult in young animals there are long-lasting functional deficits that correlate either to histological tissue damage or to potential compensatory plasticity changes. Four-week-old rats were subjected to an episode of cerebral hypoxia-ischemia (right carotid artery occlusion + 30 min of hypoxia) or a sham operation. In hypoxic-ischemic animals there were gross neurological deficits 1, 24, and 48 h postinsult with recovery by 1 week. Behavioral deficits were observed in both the acquisition and the performance of a response duration differentiation test and a fine motor control test (staircase test) 3 months after the hypoxia-ischemia. Functional magnetic resonance imaging studies demonstrated less activation in the sensory-motor cortex of hypoxic-ischemic animals in response to left vs right forepaw stimulation 4 months postinsult. Histological assessment delineated striatal, cortical, and hippocampal damage in the hypoxic-ischemic hemisphere and a reduction in cortical thickness, bilaterally. GFAP immunoreactivity was increased in injured striatum and cortex. Neurofilament heavy chain (NF200) immunoreactivity was normally most intense in white matter and decreased in areas of ipsilateral cortical damage. Synaptophysin immunoreactivity was reduced around areas of infarction and somewhat increased in adjacent undamaged striatum and in layer IV of parietal cortex. The histological damage or chronic degenerative changes could account for much of the variance in functional outcome detected with sensitive behavioral tests so that overall the compensatory or plasticity changes evident within the juvenile brain are rather modest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Conditioning, Operant
  • Electric Stimulation
  • Forelimb / physiopathology
  • Glial Fibrillary Acidic Protein / metabolism
  • Hypoxia-Ischemia, Brain / diagnosis
  • Hypoxia-Ischemia, Brain / pathology*
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Magnetic Resonance Imaging
  • Motor Skills
  • Neurofilament Proteins / metabolism
  • Neurologic Examination
  • Neuronal Plasticity
  • Predictive Value of Tests
  • Rats
  • Rats, Wistar
  • Recovery of Function
  • Sensitivity and Specificity
  • Synaptophysin / metabolism
  • Time

Substances

  • Glial Fibrillary Acidic Protein
  • Neurofilament Proteins
  • Synaptophysin
  • neurofilament protein H