Potential neuronal repair in cerebral white matter injury in the human neonate

Pediatr Res. 2011 Jan;69(1):62-7. doi: 10.1203/PDR.0b013e3181ff3792.

Abstract

Periventricular leukomalacia (PVL) in the premature infant represents the major substrate underlying cognitive deficits and cerebral palsy and is characterized as focal periventricular necrosis and diffuse gliosis in the immature cerebral white matter. We have recently shown a significant decrease in the density of neurons in PVL relative to controls throughout the white matter, including the subventricular, periventricular, and subcortical regions. These neurons are likely to be remnants of the subplate and/or GABAergic neurons in late migration to the cerebral cortex, both of which are important for proper cortical circuitry in development and throughout adulthood. Here, we tested the hypothesis that intrinsic repair occurs in PVL to attempt to compensate for the deficits in white matter neurons. By using doublecortin (DCX) immunopositivity as a marker of postmitotic migrating neurons, we found significantly increased densities (p < 0.05) of DCX-immunopositive cells in PVL cases (n = 9) compared with controls (n = 7) in the subventricular zone (their presumed site of origin), necrotic foci, and subcortical white matter in the perinatal time-window, i.e. 35-42 postconceptional weeks. These data provide the first evidence suggestive of an attempt at neuronal repair or regeneration in human neonatal white matter injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / metabolism
  • Cell Count
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Leukomalacia, Periventricular / physiopathology*
  • Microtubule-Associated Proteins / immunology
  • Microtubule-Associated Proteins / metabolism
  • Nerve Regeneration / physiology*
  • Neurons / pathology*
  • Neurons / physiology*
  • Neuropeptides / immunology
  • Neuropeptides / metabolism
  • Statistics, Nonparametric

Substances

  • Biomarkers
  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides