Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment

Preterm birth results in significant neurodevelopmental disability. A neonatal rodent model of chronic sublethal hypoxia (CSH), which mimics effects of preterm birth, was used to characterize neurodevelopmental consequences of prolonged exposure to hypoxia using tissue anisotropy measurements from diffusion tensor imaging. Corpus callosum, cingulum, and fimbria of the hippocampus revealed subtle, yet significant, hypoxia-induced modifications during maturation (P15-P51). Anisotropy differences between control and CSH mice were greatest at older ages (> P40) in these regions. Neither somatosensory cortex nor caudate putamen revealed significant differences between control and CSH mice at any age. We assessed control and CSH mice using tests of general activity and cognition for behavioral correlates of morphological changes. Open-field task revealed greater locomotor activity in CSH mice early in maturation (P16-P18), whereas by adolescence (P40-P45) differences between control and CSH mice were insignificant. These results may be associated with lack of cortical and subcortical anisotropy differences between control and CSH mice. Spatial-delayed alternation and free-swim tasks in adulthood revealed lasting impairments for CSH mice in spatial memory and behavioral laterality. These differences may correlate with anisotropy decreases in hippocampal and callosal connectivities of CSH mice. Thus, CSH mice revealed developmental and behavioral deficits that are similar to those observed in low birth weight preterm infants.