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251 LONG-TERM NEURODEVELOPMENTAL OUTCOME IN RATS AFTER HYPOXIC-ISCHEMIC INSULT.
  1. J. C. Beachy1,
  2. H. S. White1,
  3. W. L. Osterling1
  1. 1Departments of Neonatology, Pharmacology, and Neurology, University of Utah and Primary Children's Medical Center, Salt Lake City, UT.

Abstract

Background Perinatal asphyxia is a hypoxic-ischemia (H/I) insult that affects 2 to 4/1,000 live births and is associated with increased morbidity and mortality. The degree of brain damage depends on the severity and duration of the H/I insult and the maturational stage of the brain. A rat pup model of H/I insult has been developed. Exposure to 6% O2 for 1 hour results in oligodendrocyte loss, whereas exposure to 8% O2 for 2 hours results in significant neuronal necrosis and apoptosis.

Hypothesis We hypothesize that rats exposed to H/I insult will demonstrate long-term abnormal neurobehavioral sequelae, specifically alterations in motor function and pain perception.

Methods Seven-day-old Sprague-Dawley rats were subjected to unilateral carotid artery ligation and, after recovery, exposed to differing hypoxic environments (6% O2 for 1 hour or 8% O2 for 2 hours). Control rats include pups subjected to unilateral carotid artery ligation but not asphyxia, sham surgery pups, and naive pups. Motor assessment was performed by balance beam (12 in × 0.5 in) and beam walking (48 in × 5/8 in with three intermittent screws as obstacles) tests at 3 weeks of age. Plantar hotplate (30 and 70 mJ) and von Frey filament tests were used to compare thermal and mechanical allodynia at 6 weeks of age. Statistical comparisons were performed using Prism ANOVA two-way analysis of variance.

Results There was no statistically significant difference between groups or gender in balance performances. In the beam walking test, rats from all groups demonstrated improvement over time. There was no statistically significant difference between groups or gender in latency. However, subtle differences in behavior and distractibility were noted. When comparing ipsilateral to contralateral sides and comparing response between different groups, hindlimb withdrawal time due to thermal and mechanical allodynia was not statistically different.

Conclusions No statistically significant difference was noted in balance, motor coordination, or pain perception at 3 to 6 weeks after insult. Mild deficits may not be detectable with these tests. Further evaluation to correlate lesion size with testing outcomes is planned. In addition, further testing to identify subtle cognitive and behavioral differences is warranted.

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