Hypothermia treatment in Hypoxia-Inducible Factor-1α Knockout Mice with Hypoxia-Ischemia.

Introduction: Hypoxia-inducible factor-1α (HIF-1α) has a wide-ranging role in the cellular responses to hypoxia. We previously found that neuron-specific HIF-1α-deficient mice (HIF-KO) that underwent neonatal hypoxia-ischemia (HI) had increased brain injury suggesting its neuroprotective function. To investigate whether HIF-1α is also involved in the mechanisms of protection by hypothermia (HT), the standard of care for hypoxic-ischemic encephalopathy, we tested the effect of HT on HIF-KO and wild-type (WT) littermates after HI in postnatal day 9 mice.

Dysregulation of Brain Cholesterol Biosynthetic Pathway following Hypoxia Ischemia in Neonatal Mice.

Introduction: Brain cholesterol relies on de novo biosynthesis and is crucial for brain development. Cholesterol synthesis is a complex series of reactions that involves more than twenty enzymes to reach the final product and generates a large number of intermediate sterols along two alternate pathways. This is a highly regulated and oxygen-dependent process and thus sensitive to hypoxia.

Hypothermia Treatment after Hypoxia-Ischemia in Glutathione Peroxidase-1 Overexpressing Mice.

The developing brain is uniquely susceptible to oxidative stress, and endogenous antioxidant mechanisms are not sufficient to prevent injury from a hypoxic-ischemic challenge. Glutathione peroxidase (GPX1) activity reduces hypoxic-ischemic injury. Therapeutic hypothermia (HT) also reduces hypoxic-ischemic injury, in the rodent and the human brain, but the benefit is limited.