Simultaneous multinuclear NMR studies of brain metabolism

Thesis/Dissertation · Tue Dec 31 23:00:00 EST 1985

OSTI ID:6702810

Schnall, M D

The brain is a complex metabolic system with intricate interactions between the various metabolic pathways to provide the tight regulation necessary to maintain homeostasis. A major problem faced by investigators studying metabolic regulation in vivo, is the inability to noninvasively follow the evolution of changes in metabolite concentrations during imposed metabolic stress. The work described in this thesis develops in vivo NMR spectroscopy into a technique to simultaneously monitor levels of high energy phosphate metabolites, intracellular pH, lactate concentrations and ionic equilibria in a time resolved fashion, and applies this technique to study metabolic regulation in the brain. The basic technique involves frequency interleaved NMR data acquisition, allowing spectra from several nuclei to be acquired in the same time it would take to acquire a spectrum from a single nucleus. In order to permit such frequency time shared use of the NMR spectrometer, it is necessary to develop multiple tuned NMR probes, capable of operating at several different frequencies with high sensitivity. Probes using multiple-pole tuning networks and coupled tank circuits individually or in combination are described. Applications of double (/sup 31/P, /sup 1/H) and triple /sup 23/Na, /sup 1/H, /sup 31/P) nuclear NMR to study metabolic regulation in cat brain models of hypoxic ischemia and global seizure are described. The results are consistent with regulation of oxidative metabolism in the brain in vivo by the phosphorylation ratio, a potent regulator of in vitro mitochondrial function. Measurements of the brain buffering capacity and post isochemic lactate efflux are presented. A close correlation between the transmembrane Na/sup +/ gradient and the energy state is established.

• Research Organization: Pennsylvania Univ., Philadelphia (USA)
• OSTI ID: 6702810
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL ISOTOPES
ANIMALS
BARYONS
BODY
BRAIN
CARBOXYLIC ACID SALTS
CATS
CENTRAL NERVOUS SYSTEM
ELEMENTARY PARTICLES
FERMIONS
HADRONS
ISOTOPES
LACTATES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
METABOLISM
METABOLITES
NERVOUS SYSTEM
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ODD-EVEN NUCLEI
ORGANS
OXYGEN COMPOUNDS
PH VALUE
PHOSPHATES
PHOSPHORUS 31
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PROTONS
RESONANCE
SODIUM 23
SODIUM ISOTOPES
STABLE ISOTOPES
VERTEBRATES