Objective A small fraction of children born very preterm have overt cerebral palsy but many of them display subtle deficits in motor coordination, balance, and attention-deficit/hyperactivity disorder-like behavior. In the immature brain, the sudden increase of oxygen tension after birth amounts to hyperoxia, and experimental hyperoxia causes wide-ranging cerebral changes in neonatal rodents.
Methods Newborn mice were exposed to 48 h of hyperoxia (80% O2) from P6 to P8, and motor activity in running wheels was tested starting at adolescent age P30. Thereafter, from P44 to P53, regular wheels were replaced by complex wheels with variable crossbar positions to assess motor coordination. To determine white matter diffusivity, MRI with diffusion tensor imaging was performed in the corpus callosum in mice after hyperoxia at ages P30 and P53 in comparison to control animals always kept in room air.
Results Mice after neonatal hyperoxia had significantly higher values for maximum velocity and mean velocity in regular wheels than did control animals (P<0.05). In contrast, the motor challenge of the complex running wheels caused a greated decrease of maximum velocity in mice previously exposed to hyperoxia than in controls (P<0.05). Lower fractional anisotropy and higher radial diffusivity were observed in the corpus callosum of P30 and P53 mice after neonatal hyperoxia compared to control mice.
Interpretation Newborn mice exposed to hyperoxia display hyperactivity, motor coordination deficits, and impaired white matter diffusivity at adolescent and young adult ages.