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Proof of concept and feasibility studies examining the influence of combination ribose, adenine and allopurinol treatment on stroke outcome in the rat

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Faller, Kiterie M.E., Leach, Joshua, Johnston, Pamela, Holmes, William M., Macrae, I. Mhairi and Frenguelli, Bruno G. (2017) Proof of concept and feasibility studies examining the influence of combination ribose, adenine and allopurinol treatment on stroke outcome in the rat. Brain and Neuroscience Advances . ISSN 2398-2128.

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Official URL: https://doi.org/10.1177/2398212817717112

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Abstract

Background:

Cerebral ischaemia results in a rapid and profound depletion of adenosine triphosphate (ATP), the energy currency of the cell. This depletion leads to disruption of cellular homeostasis and cell death. Early replenishment of ATP levels might therefore have a neuroprotective effect in the injured brain. We have previously shown that the ATP precursors, D-ribose and adenine (RibAde), restored the reduced ATP levels in rat brain slices to values similar to those measured in the intact rodent brain. The aim of this study was to assess whether RibAde, either alone or in combination with the xanthine oxidase inhibitor allopurinol (RibAdeAll; to further increase the availability of ATP precursors), could improve outcome in an in vivo rodent model of transient cerebral ischaemia.

Methods:

After 60โ€‰min occlusion of the middle cerebral artery, and upon reperfusion, rats were administered saline, RibAde, or RibAdeAll for 6โ€‰h. Baseline lesion volume was determined by diffusion-weighted MRI prior to reperfusion and final infarct volume determined by T2-weighted MRI at Day 7. Neurological function was assessed at Days 1, 3 and 7.

Results:

Ischaemic lesion volume decreased between Days 1 and 7: a 50% reduction was observed for the RibAdeAll group, 38% for the RibAde group and 18% in the animals that received saline. Reductions in lesion size in treatment groups were accompanied by a trend for faster functional recovery.

Conclusion:

These data support the potential use of ribose, adenine and allopurinol in the treatment of cerebral ischaemic injury, especially since all compounds have been used in man.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Adenosine triphosphate, Cerebrovascular disease, Ischemia, Ribose, Adenine
Journal or Publication Title: Brain and Neuroscience Advances
Publisher: SAGE Publications
ISSN: 2398-2128
Official Date: 13 July 2017
Dates:
DateEvent
13 July 2017Published
31 May 2017Accepted
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 21 July 2017
Date of first compliant Open Access: 21 July 2017
Funder: Rosetrees Trust, University of Warwick. Development and Alumni Relations Office (DARO)
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