Hypoxia-ischemia causes persistent movement deficits in a perinatal rabbit model of cerebral palsy: assessed by a new swim test.
The relationship of movement between different muscle groups has not been quantified before in the newborn period. Cerebral palsy (CP), which often occurs as a result of perinatal hypoxia-ischemia (H-I), is categorized depending on clinical presentation, brain region involvement and extent of involvement. In order to test different brain region involvement, this study investigates individual and multi-joint involvement in a rabbit model of CP. Pregnant rabbits at 70% gestation were subjected to 40-min uterine ischemia. Newborn rabbit kits were subjected to a swim test at 5 time points over the first 11 days of life. H-I kits were divided into hypertonic and non-hypertonic groups based on muscle tone at birth. The ranges and velocity of angular movement of the forelimb and hind limb joints (wrist, elbow, shoulder, ankle, knee and hip) during supported swimming were determined. Severely impaired (hypertonic) animals have significantly reduced range and angular velocity of joint motion, which do not improve over time. The non-hypertonic group showed deficits in wrist and hind limb movements that were not evident on prolonged observation. Preventive treatment with an inhibitor of neuronal nitric oxide synthase decreased the incidence of severely impaired kits; the non-hypertonic kits showed a different pattern of swimming. Supported swimming allows quantification of limb and joint motion in the principal plane of movement in the absence of weight bearing and decreases the need for balance control. Identification and quantification of milder deficits allows mechanistic studies in the causation of H-I injury as well as estimation of recovery with therapeutic agents.
Derrick
Matthew
M
Department of Pediatrics, Northwestern University and Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201, United States. m-derrick@northwestern.edu
Drobyshevsky
Alexander
A
Ji
Xinhai
X
Chen
Lina
L
Yang
Yirong
Y
Ji
Haitao
H
Silverman
Richard B
RB
Tan
Sidhartha
S
D000818:Animals; D001696:Biomechanical Phenomena; D002547:Cerebral Palsy / Q000209:etiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005121:Extremities / Q000294:innervation / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000503:physiopathology*; D007596:Joints / Q000503:physiopathology; D008959:Models, Neurological; D009068:Movement / Q000502:physiology; D009069:Movement Disorders / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D004856:Postural Balance / Q000502:physiology; D011817:Rabbits; D016059:Range of Motion, Articular / Q000502:physiology; D013550:Swimming / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I