title: Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient changes in the peri-infarct zone during focal cerebral ischemia.
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.
authors.affiliation: Division of Health Sciences and Technology, MIT/Harvard Medical School, Cambridge and Boston, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zaharchuk
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: M C
authors.initials: MC
authors.lastname: Fishman
authors.forename: M A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: B G
authors.initials: BG
authors.lastname: Jenkins
authors.forename: B R
authors.initials: BR
authors.lastname: Rosen
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002544:Cerebral Infarction / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D004396:Coloring Agents; D004058:Diffusion; D005240:Feasibility Studies; D015971:Gene Expression Regulation, Enzymologic; D006651:Histocytochemistry; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*
chemical_list: D004396:Coloring Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase