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The purine salvage pathway and the restoration of cerebral ATP : implications for brain slice physiology and brain injury
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Frenguelli, Bruno G. (2019) The purine salvage pathway and the restoration of cerebral ATP : implications for brain slice physiology and brain injury. Neurochemical Research, 44 (3). pp. 661-675. doi:10.1007/s11064-017-2386-6 ISSN 0364-3190.
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WRAP-purine-salvage-pathway-implications-brain-physiology-Frenguelli-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2842Kb) | Preview |
Official URL: http://dx.doi.org/10.1007/s11064-017-2386-6
Abstract
Brain slices have been the workhorse for many neuroscience labs since the pioneering work of Henry McIlwain in the 1950s. Their utility is undisputed and their acceptance as appropriate models for the central nervous system is widespread, if not universal. However, the skeleton in the closet is that ATP levels in brain slices are lower than those found in vivo, which may have important implications for cellular physiology and plasticity. Far from this being a disadvantage, the ATP-impoverished slice can serve as a useful and experimentally-tractable surrogate for the injured brain, which experiences similar depletion of cellular ATP. We have shown that the restoration of cellular ATP in brain slices to in vivo values is possible with a simple combination of d-ribose and adenine (RibAde), two substrates for ATP synthesis. Restoration of ATP in slices to physiological levels has implications for synaptic transmission and plasticity, whilst in the injured brain in vivo RibAde shows encouraging positive results. Given that ribose, adenine, and a third compound, allopurinol, are all separately in use in man, their combined application after acute brain injury, in accelerating ATP synthesis and increasing the reservoir of the neuroprotective metabolite, adenosine, may help reduce the morbidity associated with stroke and traumatic brain injury.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Adenosine triphosphate, Cerebrovascular disease, Brain -- Wounds and injuries | ||||||||
Journal or Publication Title: | Neurochemical Research | ||||||||
Publisher: | Springer | ||||||||
ISSN: | 0364-3190 | ||||||||
Official Date: | March 2019 | ||||||||
Dates: |
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Volume: | 44 | ||||||||
Number: | 3 | ||||||||
Page Range: | pp. 661-675 | ||||||||
DOI: | 10.1007/s11064-017-2386-6 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 25 August 2017 | ||||||||
Date of first compliant Open Access: | 25 August 2017 | ||||||||
Funder: | Wellcome Trust (London, England), Age UK (Organization), University of Warwick. Development and Alumni Relations Office (DARO), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Rosetrees Trust |
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