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Updated: Jul 5, 2026
Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction
Published on: January 12, 2016
Early diffusion-weighted MRI as a predictor of caspase-3 activation after hypoxic-ischemic insult in neonatal rodents
Michael F Wendland1, Joel Faustino, Tim West
1University California-San Francisco, Department of Neurology, Box 0663, 521 Parnassus Ave, San Francisco, CA 94143-0663, USA.
Background And Purpose:
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.
Insights
Diffusion-weighted MRI (DWI) at 24 hours post-hypoxia-ischemia (H-I) predicts caspase-3 activation, a marker of apoptotic brain injury in neonatal rats. DWI findings indicate the presence and extent of cellular damage.
Area of Science:
- Neuroscience
- Radiology
- Cellular Biology
Background:
- Neonatal encephalopathy can cause permanent neurological deficits.
- Diffusion-weighted MRI (DWI) aids in early diagnosis of neonatal brain injury.
- The link between DWI abnormalities and cellular injury, like apoptosis, needs further understanding.
Purpose of the Study:
- To determine if DWI findings can predict caspase-3 activation, a marker of apoptotic injury, after hypoxia-ischemia (H-I) in neonatal rats.
- To investigate the relationship between the extent of injury on DWI and cellular apoptotic markers.
Main Methods:
- Hypoxia-ischemia (H-I) was induced in postnatal day 7 rats.
- Injury volume was assessed using DWI at 2, 24 hours, and 7 days post-H-I.
- Caspase-3 activation and microgliosis were measured at 24 hours post-H-I.
Main Results:
- DWI lesions at 24 hours post-H-I correlated with increased caspase-3 activity in the injured hemisphere.
- A modest increase in caspase-3 activity was observed in rats with specific DWI patterns (enlarged high ADC regions) without cortical diffusion changes.
- No significant difference in caspase-3 activity was found between hemispheres in rats with unchanged DWI.
Conclusions:
- Abnormal DWI signals at 24 hours post-H-I are predictive of caspase-3 activation, indicating apoptotic-like injury.
- DWI can serve as an indicator of injury involving apoptotic mechanisms in neonatal brain injury models.
- Specific DWI findings, such as enlarged unilateral high ADC regions, may indicate modest caspase-3 activation post-H-I.
