Document Detail


In vivo magnetization transfer MRI shows dysmyelination in an ischemic mouse model of periventricular leukomalacia.
MedLine Citation:
PMID:  21540870     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Periventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology. In vivo T2w MRI showed thinning of the right corpus callosum, but no significant changes in hippocampal and hemispheric volumes. Magnetization transfer MRI revealed significant white matter abnormalities in the bilateral corpus callosum and internal capsule. These quantitative MT-MRI changes correlated highly with postmortem findings of reduced myelin basic protein in bilateral white matter tracts. Ventriculomegaly and persistent astrogliosis were observed on the ligated side, along with evidence of axonopathy and fewer oligodendrocytes in the corpus callosum. We present an ischemia-induced mouse model of PVL, which has pathologic abnormalities resembling autopsy reports in infants with PVL. We further validate in vivo MRI techniques as quantitative monitoring tools that highly correlate with postmortem histopathology.
Authors:
Ali Fatemi; Mary Ann Wilson; Andre W Phillips; Michael T McMahon; Jiangyang Zhang; Seth A Smith; Edwin J Arauz; Sina Falahati; Abhijeet Gummadavelli; Hima Bodagala; Susumu Mori; Michael V Johnston
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-04
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  31     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2011-11-18     Revised Date:  2011-12-07    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2009-18     Citation Subset:  IM    
Affiliation:
Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland 21205, USA. fatemi@kennedykrieger.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Ischemia / metabolism,  pathology,  physiopathology,  radiography
Cerebral Palsy / metabolism,  pathology,  physiopathology,  radiography
Corpus Callosum / metabolism,  physiopathology*,  radiography*
Disease Models, Animal*
Humans
Infant, Newborn
Infant, Premature
Leukomalacia, Periventricular / metabolism,  pathology,  physiopathology*,  radiography*
Magnetic Resonance Imaging / methods*
Mice
Myelin Basic Proteins / metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
K01EB006394/EB/NIBIB NIH HHS; K08 NS063956-02/NS/NINDS NIH HHS; K08 NS063956-03/NS/NINDS NIH HHS; K08NS063956/NS/NINDS NIH HHS; R01EB003543/EB/NIBIB NIH HHS; R01NS028208/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Myelin Basic Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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