Allopregnanolone Protects Against Dopamine-Induced Striatal Damage After In Vitro Ischaemia via Interaction at GABAA Receptors

Sex steroid hormones, such as progesterone, have been shown to display neuroprotective properties after various models of central nervous system injury, including cerebral ischaemia, although the mechanism(s) of action remain largely undetermined. Allopregnanolone, an active progesterone metabolite,...

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Veröffentlicht in:Journal of neuroendocrinology 2012-08, Vol.24 (8), p.1135-1143
Hauptverfasser: Knight, S. R., Davidson, C., Young, A. M. J., Gibson, C. L.
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Sprache:eng
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Zusammenfassung:Sex steroid hormones, such as progesterone, have been shown to display neuroprotective properties after various models of central nervous system injury, including cerebral ischaemia, although the mechanism(s) of action remain largely undetermined. Allopregnanolone, an active progesterone metabolite, may explain some of the protective actions of progesterone. We utilised an in vitro model of ischaemia to evaluate the neuroprotective potential of allopregnanolone and examine its interaction at the GABAA receptor, which is hypothesised to be its main neuroprotective mechanism. In adult male mouse coronal caudate slices exposed to oxygen glucose deprivation (OGD), we measured aspects of OGD‐induced dopamine release, which is neurotoxic during ischaemia, using fast cyclic voltammetry and also assessed tissue viability. The GABAA agonist, muscimol, displayed a neuroprotective profile in terms of delaying the OGD‐evoked dopamine efflux (P 
ISSN:0953-8194
1365-2826
DOI:10.1111/j.1365-2826.2012.02319.x