The brain is critically dependent on the circulating blood for a supply of essential nutrients: glucose and ketone bodies for energy metabolism, amino acids for protein and neurotransmitters, choline for acetylcholine, and nucleosides, purines and pyrimidines for nucleotides, RNA, and DNA. The rate-limiting step for entry of each of these compounds appears to be passage across the blood-brain barrier, which is mediated by saturable transport processes obeying Michaelis-Menten kinetics. The blood-brain barrier transport systems are in a unique position to regulate the entry of essential nutrients and thereby affect brain function. It has been established at least in one pathological condition, hepatic encephalopathy, that the transport of different classes of nutrients are altered in a characteristic way. There is good reason to believe that transport in other pathological states such as diabetes, hypothyroidism, and uremia, will also be changed. Until recently, all studies examining blood-brain barrier transport have been conducted in whole brain. Further advances in our knowledge of brain function require the understanding of these processes at the structural level, and methods for achieving this have been established. It is the purpose of this proposal to study the local transport of various essential substrates at the level of individual brain structures using an autoradiographic technique developed in the principal investigator's laboratory. The primary effort will be to study the distribution of transport systems in several pathological situations including hypothyroidism, uremia, and diabetes. The data will allow the determination of the location and magnitude of changes in the blood-brain barrier and make possible the evaluation of their relevance to the disease process.
| Jessy, J; Mans, A M; DeJoseph, M R et al. (1990) Hyperammonaemia causes many of the changes found after portacaval shunting. Biochem J 272:311-7 |
| Hawkins, R A; Mans, A M (1990) Cerebral function in hepatic encephalopathy. Adv Exp Med Biol 272:1-22 |
| Mans, A M; DeJoseph, M R; Davis, D W et al. (1988) Brain energy metabolism in streptozotocin-diabetes. Biochem J 249:57-62 |
| Hibbard, L S; Hawkins, R A (1988) Objective image alignment for three-dimensional reconstruction of digital autoradiograms. J Neurosci Methods 26:55-74 |
| Hawkins, R A; Mans, A M; Hibbard, L S et al. (1988) Regional transport of some essential nutrients across the blood-brain barrier in normal and diseased states. Ann N Y Acad Sci 529:40-9 |
| Hawkins, R A; Miller, A L (1987) Deoxyglucose-6-phosphate stability in vivo and the deoxyglucose method. J Neurochem 49:1941-60 |
| McGlone, J S; Hibbard, L S; Hawkins, R A et al. (1987) A computerized system for measuring cerebral metabolism. IEEE Trans Biomed Eng 34:704-12 |
| Hawkins, R A; Mans, A M; Biebuyck, J F (1987) Changes in brain metabolism in hepatic encephalopathy. Neurochem Pathol 6:35-66 |
| Hibbard, L S; McGlone, J S; Davis, D W et al. (1987) Three-dimensional representation and analysis of brain energy metabolism. Science 236:1641-6 |
| Mans, A M; DeJoseph, M R; Davis, D W et al. (1987) Regional amino acid transport into brain during diabetes: effect of plasma amino acids. Am J Physiol 253:E575-83 |
Showing the most recent 10 out of 13 publications
