The purpose of this grant proposal is to investigate the role of the glialneuronal relationship in the process of central nervous system (CNS) elemental and ionic homeo-stasis and the effects of anesthetic agents (pentobarbital, halothane, and morphine) on that process. It is widely believed that glial cells are important to some degree in regulation of CNS elemental, water, and ionic composition. Despite considerable efforts to understand how inorganic elements and ions are moved about the CNS and how cell water is maintained, the results in this area are far from conclusive. This lack of information is due to the problems associated with making such measurements and does not reflect the importance of this fundamental information. Electron microanalysis (EPMA) of frozen hydrated tissue sections is a relatively new technique which can provide, in conjunction with ion-selective microelectrode measurements, this basic information which was not previously available using existing techniques. EPMA of frozen hydrated sections of leech (Macrobdella decora) ganglion will be used to determine the concentrations of selected intracellular elements and water content of normal glial cells and neurons. Ion- selective microelectrode measurements will be used to determine the relationship between total elemental content (measured with EPMA) and elemental activity of Na, K and Cl. The effects of ionic changes in the extracellular fluid (including Na, K, Cl, Ca, Mg, H) will be studied as well as the effects of tonicity and putative neurotransmitters (5-hydroxytryptamine and gamaaminobutyric acid). Experiments are proposed to determine the kinetics of elemental distribution and the effects of anesthetic agents on that distribution. These later experiments are designed to test the hypothesis that anesthetic agents may act by interrupting the neuron-glial interrelationship. In these experiments, anesthetics may also act as pharmacological probes useful for studying the neuronal-glial interrelationship. The results of these studies should provide previously unobtainable, fundamental information of value for basic research in neurobiology necessary to develop a more comprehensive concept of the neuron-glial interaction and its importance to CNS function. In addition, the results of these studies may also provide a basis for understanding how anesthetics work at the cellular level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021455-07
Application #
3402568
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-01-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1993-03-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
LoPachin, R M; Lehning, E J; Castiglia, C M et al. (1993) Acrylamide disrupts elemental composition and water content of rat tibial nerve. III. Recovery. Toxicol Appl Pharmacol 122:54-60
LoPachin, R M; Castiglia, C M; Lehning, E et al. (1993) Effects of acrylamide on subcellular distribution of elements in rat sciatic nerve myelinated axons and Schwann cells. Brain Res 608:238-46
LoPachin Jr, R M; Castiglia, C M; Saubermann, A J et al. (1993) Ganglioside treatment modifies abnormal elemental composition in peripheral nerve myelinated axons of experimentally diabetic rats. J Neurochem 60:477-86
Hammond, D L; Presley, R; Gogas, K R et al. (1992) Morphine or U-50,488 suppresses Fos protein-like immunoreactivity in the spinal cord and nucleus tractus solitarii evoked by a noxious visceral stimulus in the rat. J Comp Neurol 315:244-53
LoPachin, R M; Castiglia, C M; Saubermann, A J (1992) Acrylamide disrupts elemental composition and water content of rat tibial nerve. II. Schwann cells and myelin. Toxicol Appl Pharmacol 115:35-43
LoPachin, R M; Castiglia, C M; Saubermann, A J (1992) Perturbation of axonal elemental composition and water content: implication for neurotoxic mechanisms. Neurotoxicology 13:123-37
Foster, M C; Castiglia, C M; Saubermann, A J (1992) Effects of serotonin and carbachol on glial and neuronal rubidium uptake in leech CNS. Brain Res 597:181-8
Saubermann, A J; Castiglia, C M; Foster, M C (1992) Preferential uptake of rubidium from extracellular space by glial cells compared to neurons in leech ganglia. Brain Res 577:64-72
LoPachin, R M; Castiglia, C M; Saubermann, A J (1992) Acrylamide disrupts elemental composition and water content of rat tibial nerve. I. Myelinated axons. Toxicol Appl Pharmacol 115:21-34
LoPachin, R M; Castiglia, C M; Saubermann, A J (1991) Elemental composition and water content of myelinated axons and glial cells in rat central nervous system. Brain Res 549:253-9

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