Etiologies associated with neonatal hypoxic-ischemic neural injury are often unclear and outcomes are highly variable. We are utilizing an animal model to assess neurodevelopmental recovery following hypoxic-ischemic injury in neonatal rat pups. Methods: Timed-pregnant dams are received on day 2 of gestation. On postnatal day (pnd) three, pups are culled to 10 per litter, and are subjected to unilateral carotid artery ligation followed by two hours exposure to an 8% oxygen environment (Vannuci et al.) From pnd 3 through 30, pups are assessed daily for the appearance of the following neurodevelopmental milestones (Smart & Dobbing, 1971): righting reflex, cliff avoidance, negative geotaxis, auditory startle, vibrissa placing, free-fall righting and visual placing. Conduction time through the brainstem auditory pathway is measured on pnd 23 and on pnd 30. Pups are sacrificed on pnd 30, and brainstems and cerebrums are removed for morphometric analysis of auditory and vestibular brainstem pathways to identify neuronal correlates for functional findings. Results: The time of appearance of cliff avoidance, auditory startle, and visual placing is significantly delayed in pups with hypoxic-ischemic injury vs controls (p=0.033, 0.000, and 0.027 respectively). Increases in brainstem conduction time in the hypoxic-ischemic group vs the control group approach statistical significance (p=0.06). Brain morphometric analyses show a reduction in ipsilateral hemispheric volume secondary to cell loss in pups with hypoxic-ischemic injury.Conclusions: Auditory brainstem responses are an objective, highly reliable index of neural maturation at the brainstem level which can be followed from the onset of auditory function to maturity of the pathway. Milestone appearance is a relatively easy method to use in assessing neurodevelopment. This model of recovery may be useful in assessing the response of multiple levels of the central nervous system to hypoxic-ischemic injury, and to the subsequent response to various treatment modalities. Funded in part by Ross Products Division, Abbott Laboratories
