Long-term effects of neonatal ischemic-hypoxic brain injury on sensorimotor and locomotor tasks in rats.

Perinatal ischemia and/or hypoxia in humans are major risk factors for neurologic injury that often manifest as sensorimotor and locomotor deficits throughout development and into maturity. In these studies, we utilized an established model of neonatal ischemic-hypoxia that creates unilateral striatal, cortical, and hippocampal damage (Rice III, J.E., Vanucci, R.C. and Brierley, J.B., Ann. Neurol., 9 (1981) 131-141) to investigate sensorimotor and locomotor deficits in these animals during development and as adults. Sensorimotor deficits were examined by measuring the amount of time that the animals were able to remain on a rotating treadmill. Locomotor abnormalities were assessed by measuring apomorphine-induced rotational asymmetry. Following the neonatal ischemic-hypoxic episode, at 3-9 weeks of age, animals were not able to remain on the treadmill as long as their normal littermate controls. In addition, these animals demonstrated an abnormal, ipsiversive rotational asymmetry in response to systemic administration of apomorphine. When these animals reached adulthood, the degree of atrophy in specific regions of the damaged hemisphere was quantified using measurements of cross-sectional area. The mean cross-sectional area of the striatum was decreased by 29%, the sensorimotor cortex area by 26%, and the dorsal hippocampus cross-sectional area was approximately 6% of its normal size. These data suggest that this rodent model of neonatal ischemic-hypoxic brain injury results in cerebral atrophy and long-lasting sensorimotor and locomotor deficits. These particular behavioral tasks may be used in future studies to assess locomotor and sensorimotor deficits following neonatal ischemic-hypoxic brain injury.