Adult neurological function following neonatal hypoxia-ischemia in a mouse model of the term neonate: water maze performance is dependent on separable cognitive and motor components

Abstract

Background and purpose: Hypoxic-ischemic injury in term neonates remains a significant cause of long-term neurological morbidity. The post-natal day 10 (P10) mouse is accepted as a model for the term human. This study was designed to assess the relationships between the duration of hypoxia-ischemia (HI) on P10 and the structural and functional neurological deficits that appear in the adult mouse as a consequence.

Methods: Post-natal day 10 129T2xC57Bl/6 F1 hybrid mice were subjected to 0, 45, 60 or 75 min of hypoxia-ischemia using the Rice-Vannucci model. Beginning on P50 these mice were tested over the next 8 weeks using zero maze, locomotor activity, novel object recognition, cued, hidden and reduced Morris water mazes, delayed probe trials and response to apomorphine injection. Brain weights and histology were obtained at the end of testing.

Results: The degree of structural and behavioral abnormalities in adult mice correlated with the duration of hypoxia-ischemia on P10. Useful behavioral tests for separating adult mice according to duration of hypoxia-ischemia on P10 include locomotor activity, the Morris water mazes and response to apomorphine. We found cued "learning" persisted, although latencies increased, with increasing HI time while spatial learning decayed as a function of HI time. Severe HI injury involving the ventral hippocampus resulted in excessive locomotor activity.

Conclusions: After correcting for motor deficits, there is evidence for persistence of "cued" learning but not spatial learning with increasing hypoxia-ischemia time on P10 in this model system.