Brain Energetics and Tolerance to Anoxia in Deep Hypothermia

Abstract

The remarkable time-resolution enhancement by deep lethargic hypothermia (15 degrees C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo (31)P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.

Preclinical 1 H-Mrs Neurochemical Profiling in Neurological And Psychiatric Disorders

“…Its main disadvantage – low sensitivity – is inseparable from its main advantage – non-invasive interrogation. In addition to the non-invasive probing of in vivo chemical compositions, MRS is useful in various studies of the brain, primarily for its ability to detect subtle physicochemical changes in neurological tissue, such as intracellular pH [16] or molecule dynamics [17–19]. Analyzed subjects can be scanned repetitively, since exposure is limited to nonionizing electromagnetic field and magnetic field gradients without known hazards.…”

“…Another possibility is to increase spin polarization. Recent developments in hyperpolarization have opened an avenue for wider in vivo use of other nuclei [16,17]. …”

Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals

“…15). 61 While the spatial resolution with this technique is lower than that of proton MRS, phosphorous MRS can provide important information about energy metabolites, including inorganic phosphorous, phosphocreatine, and ATP (␥, ␣, and ␤ peaks) (FIG. 16); it can also be used for in vivo pH measurement.…”

“…60 Phosphorous MRS studies can also be used to study energy metabolites. 61 Experimental stroke models in small rodents are frequently studied with MRI methods. These generally re- quire classic MR imaging modalities, including T1, T2, and proton density imaging.…”

MRI in Rodent Models of Brain Disorders

“…MRI has the capability of studying live organisms without exposing them to potentially harmful ionizing radiation. Besides anatomical imaging, MRI is also capable of providing physiological information about several important aspects of biological processes, including circulation and cerebrospinal fluid flow, cerebral blood flow and volume, activity mapping with functional MRI (fMRI) or Mn ++ -based techniques, metabolite distribution with chemical shift imaging, diffusion or perfusion properties of the studied tissue, or in vivo pH measurement via phosphorus MR spectrometry (MRS) [2,3].…”