Late measures of brain injury after neonatal hypoxia-ischemia in mice.
OBJECTIVE
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.
Ten
Vadim S
VS
Department of Pediatrics, Columbia University, New York, NY, USA.
Wu
Ed X
EX
Tang
Haiying
H
Bradley-Moore
Maria
M
Fedarau
Maksim V
MV
Ratner
Veniamin I
VI
Stark
Raymond I
RI
Gingrich
Jay A
JA
Pinsky
David J
DJ
D000818:Animals; D000831:Animals, Newborn; D001259:Ataxia / Q000209:etiology* / Q000473:pathology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology; D017536:Carotid Artery, Common; D002552:Cerebral Ventricles / Q000473:pathology; D003560:Cysts / Q000209:etiology / Q000473:pathology; D005106:Exploratory Behavior; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000473:pathology; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology; D008026:Ligation; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009473:Neuronal Plasticity; D009483:Neuropsychological Tests