Related Experiment Videos
Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient
G Zaharchuk1, H Hara, P L Huang
1Division of Health Sciences and Technology, MIT/Harvard Medical School, Cambridge and Boston, MA, USA.
Abstract:
Diffusion-weighted MRI at 2 T was used to monitor and assess tissue damage after permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and mice deficient in nitric oxide synthase gene expression (nNOS-). The ischemic lesion was evaluated 3 h after occlusion and subdivided into the lesion core and peri-infarct zone based on the magnitude of the apparent diffusion coefficient (ADC) change. Infarct volume, measured by using histochemical staining 24 h after MCA occlusion, correlated best with MRI infarct volume as assessed by an ADC threshold of 25% decrease from baseline at 3 h. For ADC thresholds of greater than 25% decrease, lesion size was not significantly different in nNOS- and WT mice. However, brain tissue showing ADC decreases of 10-25% was significantly smaller in the ipsilateral hemisphere of mutants (27 +/- 2% and 21 +/- 2% in WT and nNOS-, respectively; P < 0.05). These findings occurred independently of infarct volume and are consistent with a smaller peri-infarct zone in nNOS- mice. We postulate that the smaller peri-infarct zone is a reflection of less severe metabolic disturbance after ischemia in nNOS- mice, possibly related to diminished production of nitric oxide (NO) or a related product. We conclude that magnetic resonance techniques previously used to assess ischemic damage in larger animals can be extended to the mouse, raising the possibility that the molecular mechanisms leading to ischemic damage can be examined by using genetically engineered mice.
Insights
Mice lacking nitric oxide synthase gene expression show a smaller peri-infarct zone after middle cerebral artery occlusion, suggesting reduced metabolic disturbance. Diffusion-weighted MRI effectively assesses ischemic damage in mice.
Area of Science:
- Neuroscience
- Medical Imaging
- Molecular Biology
Background:
- Permanent middle cerebral artery occlusion (MCAO) is a model for ischemic stroke.
- Nitric oxide synthase (NOS) plays a role in regulating cerebral blood flow and neuronal function during ischemia.
- Understanding the role of NOS in ischemic stroke is crucial for developing targeted therapies.
Purpose of the Study:
- To assess tissue damage and lesion development after MCAO in wild-type (WT) and nNOS-deficient mice using diffusion-weighted MRI.
- To investigate the correlation between MRI-derived infarct volume and histochemical measurements.
- To determine if nNOS deficiency influences the size of the ischemic lesion core and peri-infarct zone.
Main Methods:
- Diffusion-weighted MRI at 2 Tesla was employed to monitor ischemic damage.
- The study involved permanent middle cerebral artery occlusion in WT and nNOS-deficient mice.
- Lesion core and peri-infarct zones were defined based on apparent diffusion coefficient (ADC) changes.
- Infarct volume was confirmed using histochemical staining 24 hours post-occlusion.
Main Results:
- Infarct volume measured by MRI correlated well with histochemical staining using a 25% ADC decrease threshold.
- No significant difference in lesion size was observed between WT and nNOS- mice for ADC decreases >25%.
- A significantly smaller peri-infarct zone (10-25% ADC decrease) was found in nNOS- mice compared to WT mice (21% vs. 27%).
Conclusions:
- Diffusion-weighted MRI techniques are applicable for assessing ischemic damage in mouse models.
- Mice deficient in nNOS exhibit a reduced peri-infarct zone, indicating less severe metabolic disturbance post-ischemia.
- This suggests a potential protective role for diminished nitric oxide production in ischemic stroke, warranting further investigation into molecular mechanisms.