White matter injury correlates with hypertonia in an animal model of cerebral palsy.
Hypertonia and postural deficits are observed in cerebral palsy and similar abnormalities are observed in postnatal rabbits after antenatal hypoxia-ischemia. To explain why some kits become hypertonic, we hypothesized that white matter injury was responsible for the hypertonia. We compared newborn kits at postnatal day 1 (P1) with and without hypertonia after in vivo global fetal hypoxia-ischemia in pregnant rabbits at 70% gestation. The aim was to examine white matter injury by diffusion tensor magnetic resonance imaging indices, including fractional anisotropy (FA). At P1, FA and area of white matter were significantly lower in corpus callosum, internal capsule, and corona radiata of the hypertonic kits (n=32) than that of controls (n=19) while nonhypertonic kits (n=20) were not different from controls. The decrease in FA correlated with decrease in area only in hypertonia. A threshold of FA combined with area identified only hypertonic kits. A reduction in volume and loss of phosphorylated neurofilaments in corpus callosum and internal capsule were observed on immunostaining. Concomitant hypertonia with ventriculomegaly resulted in a further decrease of FA from P1 to P5 while those without ventriculomegaly had a similar increase of FA as controls. Thus, hypertonia is associated with white matter injury, and a population of hypertonia can be identified by magnetic resonance imaging variables. The white matter injury manifests as a decrease in the number and density of fiber tracts causing the decrease in FA and volume. Furthermore, the dynamic response of FA may be a good indicator of the plasticity and repair of the postnatal developing brain.
Drobyshevsky
Alexander
A
Department of Pediatrics, Evanston Northwestern Healthcare and Northwestern University, Evanston, Illinois 60201, USA. oldrobys@northwestern.edu
Derrick
Matthew
M
Wyrwicz
Alice Mary
AM
Ji
Xinhai
X
Englof
Ila
I
Ullman
Lauren Marie
LM
Zelaya
Mario Enrique
ME
Northington
Frances Josephine
FJ
Tan
Sidhartha
S
D000818:Animals; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D002547:Cerebral Palsy / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D000860:Hypoxia / Q000503:physiopathology; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D009122:Muscle Hypertonia / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits
D016900:Neurofilament Proteins