Diffusion characteristics associated with neuronal injury and glial activation following hypoxia-ischemia in the immature brain

Gregory A. Lodygensky, Tim West, Matthew D. Moravec, Stephen Back, Krikor Dikranian, David M. Holtzman, Jeffrey J. Neil

Research output: Contribution to journalArticle

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Abstract

To identify quantitative MRI indices of injury in the brain following neonatal hypoxic-ischemic brain injury, we subjected mouse pups to hypoxia-ischemia on postnatal day 7 and obtained conventional and diffusion-weighted in vivo images of the brain 24 h later followed by histological assessment. T 2-weighted images showed increased signal intensity in the CA1 and CA2 regions of the hippocampus ipsilateral to the injury and adjacent white matter. In contrast, diffusion imaging showed reduced apparent diffusion coefficient (ADC) values in CA1 and CA2, but increased values in the adjacent white matter. Histological analysis showed widespread gliosis with degenerating oligodendrocytes in the ipsilateral hippocampus. In addition, white matter areas that were abnormal by MRI showed an increase in the number of activated microglia (CD45 positive cells). Activated caspase-3 immunostaining showed a marked increase in neurons in the hippocampal regions corresponding to those with reduced ADC, and a quantitative measure of staining showed a statistically significant correlation with the ADC. In contrast, ADC was higher in adjacent white matter, where histology showed activation of microglia and reactive oligodendrocytes but not caspase-3 activation. These results suggest that the ADC response differs between areas of neuronal injury as compared with those showing glial changes without marked cell death.

Original languageEnglish (US)
Pages (from-to)839-845
Number of pages7
JournalMagnetic Resonance in Medicine
Volume66
Issue number3
DOIs
StatePublished - Sep 2011

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Neuroglia
Ischemia
Wounds and Injuries
Brain
Oligodendroglia
Microglia
Caspase 3
Brain Injuries
Hippocampus
Gliosis
Hypoxia
Histology
Cell Death
Staining and Labeling
Neurons
White Matter

Keywords

  • apoptosis
  • apparent diffusion coefficient
  • caspase-3 activation
  • hypoxic-ischemic injury

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Diffusion characteristics associated with neuronal injury and glial activation following hypoxia-ischemia in the immature brain. / Lodygensky, Gregory A.; West, Tim; Moravec, Matthew D.; Back, Stephen; Dikranian, Krikor; Holtzman, David M.; Neil, Jeffrey J.

In: Magnetic Resonance in Medicine, Vol. 66, No. 3, 09.2011, p. 839-845.

Research output: Contribution to journalArticle

Lodygensky, Gregory A. ; West, Tim ; Moravec, Matthew D. ; Back, Stephen ; Dikranian, Krikor ; Holtzman, David M. ; Neil, Jeffrey J. / Diffusion characteristics associated with neuronal injury and glial activation following hypoxia-ischemia in the immature brain. In: Magnetic Resonance in Medicine. 2011 ; Vol. 66, No. 3. pp. 839-845.
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