Preclinical validation of the therapeutic potential of Glasgow Oxygen Level Dependent (GOLD) technology: A theranostic for acute stroke

Deuchar, G. A., Van Kralingen, J. C., Work, L. M. , Santosh, C., Muir, K. W. , McCabe, C. and Macrae, I. M. (2019) Preclinical validation of the therapeutic potential of Glasgow Oxygen Level Dependent (GOLD) technology: A theranostic for acute stroke. Translational Stroke Research, 10(5), pp. 583-595. (doi: 10.1007/s12975-018-0679-y) (PMID:30506268)

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Abstract

In acute stroke patients, penumbral tissue is non-functioning but potentially salvageable within a time window of variable duration and represents target tissue for rescue. Reperfusion by thrombolysis and/or thrombectomy can rescue penumbra and improve stroke outcomes, but these treatments are currently available to a minority of patients. In addition to the utility of Glasgow Oxygen Level Dependent (GOLD) as an MRI contrast capable of detecting penumbra, its constituent perfluorocarbon (PFC) oxygen carrier, combined with normobaric hyperoxia, also represents a potential acute stroke treatment through improved oxygen delivery to penumbra. Preclinical studies were designed to test the efficacy of an intravenous oxygen carrier, the perfluorocarbon emulsion Oxycyte® (O-PFC), combined with normobaric hyperoxia (50% O2) in both in vitro (neuronal cell culture) and in vivo rat models of ischaemic stroke. Outcome was assessed through the quantification of lipid peroxidation and oxidative stress levels, mortality, infarct volume, neurological scoring and sensorimotor tests of functional outcome in two in vivo models of stroke. Additionally, we investigated evidence for any positive or negative interactions with the thrombolytic recombinant tissue plasminogen activator (rt-PA) following embolus-induced stroke in rats. Treatment with intravenous O-PFC + normobaric hyperoxia (50% O2) provided evidence of reduced infarct size and improved functional recovery. It did not exacerbate oxidative stress and showed no adverse interactions with rt-PA. The positive results and lack of adverse effects support human trials of O-PFC + 50% O2 normobaric hyperoxia as a potential therapeutic approach. Combined with the diagnostic data presented in the preceding paper, O-PFC and normobaric hyperoxia is a potential theranostic for acute ischaemic stroke.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Deuchar, Dr Graeme and Macrae, Professor I Mhairi and Van Kralingen, Ms Josie and Santosh, Dr Celestine and Muir, Professor Keith and McCabe, Dr Chris and Work, Dr Lorraine
Authors: Deuchar, G. A., Van Kralingen, J. C., Work, L. M., Santosh, C., Muir, K. W., McCabe, C., and Macrae, I. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Translational Stroke Research
Publisher:Springer Verlag
ISSN:1868-4483
ISSN (Online):1868-601X
Published Online:30 November 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Translational Stroke Research 10(5):583-595
Publisher Policy:Reproduced under a Creative Commons License

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