on July 22, 2004
Published online before print July 22, 2004, doi: 10.1161/01.STR.0000137768.25203.df
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Submitted on February 23, 2004
From the Departments of Pediatrics (V.S.T., V.I.R., R.I.S.), Radiology (E.X.W., H.T.), Developmental Psychobiology (M.B.-M.), and Psychiatry (J.A.G.), Columbia University, New York, NY; and the Department of Medicine (M.V.F., D.J.P.), University of Michigan, Ann Arbor, Mich. * To whom correspondence should be addressed. E-mail: dpinsky{at}umich.edu.
Background and Purpose--This work was undertaken to determine to what degree long-term neurofunctional outcome of neonatal hypoxic-ischemic (HI) brain injury in mice correlates with anatomical extent of cerebral damage assessed by magnetic resonance imaging (MRI) and histopathology. Methods--On postnatal day 7, mice were subjected to HI. At 7 to 9 weeks after HI neurofunctional outcome was assessed by water-maze, rota-rod, and open-field test performance, followed by cerebral MRI and histopathology evaluation. Results--At 10 weeks after HI, MRI revealed ipsilateral brain atrophy alone or with porencephalic cyst formation and contralateral ventriculomegaly. Adult HI-affected mice, especially those that developed a porencephalic cyst, demonstrated significant neurofunctional deficit compared with age-matched naïve mice. HI-affected mice with ipsilateral cerebral atrophy but without porencephaly demonstrated no or an intermediate level of neurofunctional deficit. Neurobehavioral assessment of mice subjected to HI insult revealed a strong correlation between degree of brain injury and functional neurohandicap. Conclusions--This is the first study to demonstrate that long-term neurofunctional outcome in mice after a neonatal HI correlates tightly with anatomical pattern/extent of cerebral damage, defined by MRI and histopathology.
Revised on April 21, 2004
Accepted on May 21, 2004
Late Measures of Brain Injury After Neonatal Hypoxia-Ischemia in Mice
Vadim S. Ten MD, PhD;
Key words: hypoxia • ischemia • animals, newborn • mice
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