Biliverdin is converted into bilirubin which protects blood vessels and neurons from oxidant stress as occurs in ischemia. These mechanisms of vascular regulation and neuroprotection by hemoglobin solutions and heme oxygenase by-products are being investigated experimentally in vivo and in cell culture. A third project utilizes an animal model of neonatal hypoxic-ischemic encephalopathy to understand the mechanisms by which selective regions of the neonatal brain are selectively vulnerable to asphyxic insults. Hypothermia and various pharmacological therapies are being tested. A fourth project utilizes an animal model to study cerebrovascular regulation during prenatal and postnatal development and during the transition at birth.
Emphasis is on oxygen-dependent mechanisms of cerebrovascular regulation.
In a fifth project, the mechanisms by which elevated plasma ammonia, as occurs in liver disease and certain inborn errors of metabolism, causes brain swelling and impaired cerebrovascular regulation are being evaluated. Experiments focus on ammonia metabolism and glutamine formation in astrocytes as a mechanism of astrocyte swelling and impaired potassium regulation, and on the interaction of glutamine with arginine on nitric oxide dependent vasodilation.