We are involved in two projects. The first is the transport of essential nutrients across the blood-brain barrier using isolated cell constituents in vitro
and autoradiography in vivo
. Our focus has been on glucose and amino acid carriers in the constituent membranes of the blood-brain barrier, as well as those in intracellular pools. Both the luminal and abluminal membranes of endothelial cells, which constitute the blood-brain barrier, are isolated as vesicles, and various measurements made. We are testing the hypothesis that the distribution, ion dependency, and kinetics of transport proteins favor the delivery of glucose and essential amino acids to the brain, but prevent accumulation of nonessential amino acids that may serve as neurotransmitters.
The second subject is hepatic encephalopathy, a significant cause of morbidity and mortality worldwide that is caused by elevated ammonia in circulation when blood bypasses the liver. We showed that reducing the incorporation of ammonia into brain glutamine could mitigate the disease and possibly reverse it. The remaining work to be done is to provide definitive evidence that inhibiting brain glutamine synthetase activity can prevent hepatic encephalopathy long-term, and that inhibiting brain glutamine synthetase activity can reverse established hepatic encephalopathy