title: Age-dependent exacerbation of white matter stroke outcomes: a role for oxidative damage and inflammatory mediators.
abstract: OBJECTIVE
  Subcortical white matter stroke (WMS) constitutes up to 30% of all stroke subtypes. Mechanisms of oligodendrocyte and axon injury and repair play a central role in the damage and recovery after this type of stroke, and a comprehensive study of these processes requires a specialized experimental model that is different from common large artery, gray matter stroke models. Diminished recovery from stroke in aged patients implies that damage and repair processes are affected by advanced age, but such effects have not been studied in WMS.
  
  
  METHODS
  WMS was produced with focal microinjection of the vasoconstrictor N5-(1-iminoethyl)-L-ornithine into the subcortical white matter ventral to the mouse forelimb motor cortex in young adult (2 months), middle-aged (15 months), and aged mice (24 months).
  
  
  RESULTS
  WMS produced localized oligodendrocyte cell death with higher numbers of apoptotic cells and greater oxidative damage in aged brains than in young-adult brains. Increased expression of monocyte chemotactic protein-1 and tumor necrosis factor-α in motor cortex neurons correlated with a more distributed microglial activation in aged brains 7 days after WMS. At 2 months, aged mice displayed increased white matter atrophy and greater loss of corticostriatal connections compared with young-adult mice. Behavioral testing revealed an age-dependent exacerbation of forelimb motor deficits caused by the stroke, with decreased long-term functional recovery in aged animals.
  
  
  CONCLUSIONS
  Age has a profound effect on the outcome of WMS, with more prolonged cell death and oxidative damage, increased inflammation, greater secondary white matter atrophy, and a worse behavioral effect in aged versus young-adult mice.
authors.affiliation: Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Shira
authors.initials: S
authors.lastname: Rosenzweig
authors.forename: S Thomas
authors.initials: ST
authors.lastname: Carmichael
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001284:Atrophy; D054022:Cerebrum / Q000473:pathology*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000502:physiology*; D056784:Leukoencephalopathies / Q000139:chemically induced / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009836:Oligodendroglia / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000139:chemically induced / Q000150:complications / Q000473:pathology*
chemical_list: D018836:Inflammation Mediators
keywords: aging; axonal degeneration; inflammation; oligodendroglia; oxidative stress; stroke; white matter