Two models for determining the mechanisms of damage and repair after hypoxic-ischaemic injury in the developing rat brain

The ability to induce either selective neuronal loss or pannecrosis provides an opportunity to investigate the mechanisms of damage or recovery associated with each pattern of cell loss, and two preparations were developed for ease of preparation, consistent neuronal loss scores and low mortality.

Abstract

Hypoxic-ischaemic (HI) brain injury can lead to selective neuronal loss or pannecrosis. Different mechanisms of damage and recovery may be associated with either pattern of cell loss. Two preparations were developed to investigate the role of growth factors and other mechanisms associated with either of these patterns of damage in the developing brain. Twenty-one-day-old Wistar rats underwent permanent unilateral right carotid artery ligation. Following surgery, ligated rats were warmed for 2 h at 34 degrees C with 85 +/- 5% relative humidity and then exposed to either 15 or 60 min of 8% O2. The rats were killed and brains perfusion fixed 5 days post-hypoxia for histological analysis. Rats exposed to 15 min of hypoxia-ischaemia suffered no mortality and 90% developed selective neuronal loss in the frontoparietal cortex and hippocampal CA1 region of the ipsilateral hemisphere. Rats exposed to 60 min of hypoxia consistently developed cortical pannecrosis and cellular loss in the striatum, thalamus, hippocampus and dentate gyrus of the ipsilateral hemisphere. The advantage of these models were ease of preparation, consistent neuronal loss scores and low mortality. The ability to induce either selective neuronal loss or pannecrosis provides an opportunity to investigate the mechanisms of damage or recovery associated with each pattern of cell loss.