Neuroprotection of the Βeta-Hydroxybutyrate in Hypoxia Piglet Brains

Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent neurological dysfunction in children. Despite recent advances in understanding the pathogenesis of neonatal HI brain injury, currently, there is no effective treatment. The present study was conducted to test the hypothesis that the hypoxia-induced multiple mechanism in the cerebral cortex of newborn piglets is blocked by β-hydroxybutyrate. We use the animal model of the cerebral cortex of newborn piglets after hypoxia (10%O2) for 30min to test the neuroprotective effect ofβ-hydroxybutyrate. In this animal model, hypoxia can induce neuronal injury by increased mitochondrial calcium, and then lead to increased reactive oxygen species (ROS), decreased synthesis of ATP, and following to open the mitochondrial permeability transition pore (mPTP). As a result, cytochrome c (cyt c) is released into the cytoplasm and initiates the apoptotic cascade. β-hydroxybutyrate is one component of ketone body。β-hydroxybutyrate have the possible multiple mechanism, included increasing calbindin which buffer mitochondrial calcium, promoting mitochondrial biogenesis (which increases ATP synthesis), and activating uncoupling proteins (which decreases ROS formation), and inhibits apoptotic factors (Bad, capsase 3). So β-hydroxybutyrate had multiple mechanism of neuroprotective properties. So we use the animal model of the cerebral cortex of newborn piglets after hypoxia (10%O2) for 30min to test the neuroprotective effect ofβ-hydroxybutyrate by multiple mechanism.

Project ID:PC9907-2529
External Project ID:NSC99-2314-B182-025