Early diffusion-weighted MRI as a predictor of caspase-3 activation after hypoxic-ischemic insult in neonatal rodents.
OBJECTIVE
Neonatal encephalopathy in human babies is a serious condition associated with permanent neurological deficits. Diffusion-weighted MRI (DWI) is increasingly used for early diagnosis of brain injury in human babies. The relationship between the presence of DWI abnormalities and cellular injury, including apoptosis, during the neonatal period are not well understood. We asked whether the extent of injury depicted on DWI can predict the presence of caspase-3 activation, a quantitative marker of apoptotic injury, after hypoxia-ischemia (H-I) in postnatal day 7 rats.


METHODS
Injury volume was determined by DWI at 2 hours, 24 hours, and 7 days after H-I and compared with histology. Caspase-3 activation and microgliosis were determined at 24 hours post-H-I.


RESULTS
DWI-defined lesions (eg, decreased apparent diffusion coefficient) at 24 hours post-H-I correlated with a major increase in caspase-3 activity in the injured hemisphere and predicted injury. A modest but significant increase in caspase-3 activity occurred in the cortex of rats that had no apparent diffusion coefficient decrease in the injured hemisphere but had unilaterally enlarged regions of high apparent diffusion coefficient at the ipsilateral ventricle/white matter interface. Caspase-3 activity was similar in both hemispheres in pups with unchanged DWI.


CONCLUSIONS
Abnormal DWI signal at 24 hours post-H-I is predictive of caspase-3 activation and can be used as an indicator that injury involving an apoptotic-like mechanism is present. Our data also suggest that the presence of an enlarged unilateral region with high apparent diffusion coefficient at the ventricle/white matter interface without significant apparent diffusion coefficient decrease in the cortex is a sign of modest caspase-3 activation after H-I.
Wendland
Michael F
MF
University California-San Francisco, Department of Neurology, Box 0663, 521 Parnassus Ave, San Francisco, CA 94143-0663, USA.
Faustino
Joel
J
West
Tim
T
Manabat
Catherine
C
Holtzman
David M
DM
Vexler
Zinaida S
ZS
D000818:Animals; D000831:Animals, Newborn; D016880:Anisotropy; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000473:pathology*; D020520:Brain Infarction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; D053148:Caspase 3