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

Faller, K. M.E., Leach, J., Johnston, P. , Holmes, W. M. , Macrae, I. M. and Frenguelli, B. 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, 1, pp. 1-13. (doi: 10.1177/2398212817717112)

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 60min occlusion of the middle cerebral artery, and upon reperfusion, rats were administered saline, RibAde, or RibAdeAll for 6h. 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: Articles
• Additional Information: This work was funded by grants from the Rosetrees Trust and from Warwick University Alumni Fund.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leach, Dr Joshua and Macrae, Professor Mhairi and Holmes, Dr William and Faller, Ms Kiterie and Johnston, Dr Pamela
• Authors: Faller, K. M.E., Leach, J., Johnston, P., Holmes, W. M., Macrae, I. M., and Frenguelli, B. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Brain and Neuroscience Advances
• Publisher: SAGE Publications
• ISSN: 2398-2128
• ISSN (Online): 2398-2128
• Published Online: 13 July 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Brain and Neuroscience Advances 1: 1-13
• Publisher Policy: Reproduced under a Creative Commons License