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7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischaemia-induced neuronal damage both in vivo and in vitro

Pringle, Ashley K., Schmidt, Werner, Deans, Jackie K., Wulfert, Ernst, Reymann, Klaus G. and Sundstrom, Lars E. (2003) 7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischaemia-induced neuronal damage both in vivo and in vitro European Journal of Neuroscience, 18, (1), pp. 117-124. (doi:10.1046/j.1460-9568.2003.02734.x).

Record type: Article

Abstract

Recent evidence suggests that steroids such as oestradiol reduce ischaemia-induced neurodegeneration in both in vitro and in vivo models. A cytochrome P450 enzyme termed cyp7b that 7-hydroxylates many steroids is expressed at high levels in brain, although the role of 7-hydroxylated steroids is unknown. We have tested the hypothesis that the steroid-mediated neuroprotection is dependent on the formation of 7-hydroxy metabolites. Organotypic hippocampal slice cultures were prepared from Wistar rat pups and maintained in vitro for 14 days. Cultures were then exposed to 3 h hypoxia and neuronal damage assessed 24 h later using propidium iodide fluorescence as a marker of cell damage. Neurodegeneration occurred primarily in the CA1 pyramidal cell layer. The steroids oestradiol, dehydroepiandrosterone and epiandrosterone (EPIA) were devoid of neuroprotective efficacy when present at 100 nm pre-, during and post-hypoxia. The 7-hydroxy metabolites of EPIA, 7?-OH-EPIA and 7?-OH-EPIA significantly reduced neurotoxicity at 100 nm and 10 nm. 7?-OH-EPIA was also neuroprotective in two in vivo rat models of cerebral ischaemia: 0.1 mg/kg 7?-OH-EPIA significantly reduced hippocampal cell loss in a model of global forebrain ischaemia, whereas 0.03 mg/kg was neuroprotective in a model of focal ischaemia even when administration was delayed until 6 h after the onset of ischaemia. Taken together, these data demonstrate that 7-hydroxylation of steroids confers neuroprotective efficacy, and that 7?-OH-epiandrosterone represents a novel class of neuroprotective compounds with potential for use in acute neurodegenerative diseases.

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Published date: July 2003

Identifiers

Local EPrints ID: 27691
URI: http://eprints.soton.ac.uk/id/eprint/27691
ISSN: 0953-816X
PURE UUID: e7b7829c-7127-48e1-8f67-14aaefe03449
ORCID for Ashley K. Pringle: ORCID iD orcid.org/0000-0003-2421-4380

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Date deposited: 28 Apr 2006
Last modified: 17 Jul 2017 16:04

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Contributors

Author: Werner Schmidt
Author: Jackie K. Deans
Author: Ernst Wulfert
Author: Klaus G. Reymann
Author: Lars E. Sundstrom

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