TY - JOUR
T1 - Diffusion characteristics associated with neuronal injury and glial activation following hypoxia-ischemia in the immature brain
AU - Lodygensky, Gregory A.
AU - West, Tim
AU - Moravec, Matthew D.
AU - Back, Stephen A.
AU - Dikranian, Krikor
AU - Holtzman, David M.
AU - Neil, Jeffrey J.
PY - 2011/9
Y1 - 2011/9
N2 - 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. T2-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.
AB - 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. T2-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.
KW - apoptosis
KW - apparent diffusion coefficient
KW - caspase-3 activation
KW - hypoxic-ischemic injury
UR - http://www.scopus.com/inward/record.url?scp=79961072233&partnerID=8YFLogxK
U2 - 10.1002/mrm.22869
DO - 10.1002/mrm.22869
M3 - Article
C2 - 21394776
AN - SCOPUS:79961072233
SN - 0740-3194
VL - 66
SP - 839
EP - 845
JO - Magnetic resonance in medicine
JF - Magnetic resonance in medicine
IS - 3
ER -