Neuroprotective intervention after hypoxia-ischemia may change intracerebral metabolic measures in a newborn piglet model

Introduction Hypoxic-Ischemic Neonatal Encephalopathy (HIE) is a major contributor to neurological impairment and death in children. Due to the similarity with the human brain, newborn piglets are often used in studies of new treatments for HIE. Cell death after hypoxia ischemia (HI) occurs in stages, each offering different targets for interventions. Therapeutic hypothermia (TH) is the only treatment for HIE. We hope to provide knowledge concerning the metabolic processes occurring in the brain after HI. The aim of this study was to quantify changes in intracerebral metabolism, pressure, flow, and oxygen saturation after HI in controls and TH piglets. We present preliminary data from the first animals. Materials and Methods Piglets (<24 hours old) were anaesthetized, intubated and ventilated. Two probes and one microdialysis catheter were inserted 10 mm into the left parasagittal cortex. Probes measured intracranial pressure (ICP), flow, temperature, and oxygen tension. By microdialysis we measured lactate, glucose, glycerol, and pyruvate. A NIRS-probe was placed on the right side of the head and aEEG electrodes were placed on each side. After 24 hours of stabilisation, HI was induced for 45 minutes. Piglets were randomized to either TH (rectal temperature of 33.5 C) or normothermia and intracerebral measures were taken every hour for 48 consecutive hours. TH was initiated immediately after HI and was continued for the 48 hours. Results Preliminary results from two controls and one piglets subjected to HI are presented. The HI piglet was randomized to normothermia. All measures described were successfully recorded. Controls showed unaffected intracerebral measures. In the HI piglet, glycerol increased through the whole observation period, while lactate plateaued after approximately 24 hours. Lactate/pyruvate ratio and ICP showed a parabolic pattern in the HI piglet. Conclusion We present a novel take on an already well-established animal model for HIE. We expect to provide basic knowledge of how interventions may affect intracerebral metabolic measures, pressure and gas-exchange. These measures may also guide optimal timing of potential new treatments.