Journal
NEUROPHARMACOLOGY
Volume 62, Issue 2, Pages 1082-1090Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2011.10.022
Keywords
Galantamine; Ischemia; Neuroprotection; ROS
Categories
Funding
- Spanish Ministry of Science and Innovation [SAF2009-12150]
- Spanish Ministry of Health (Instituto de Salud Carlos III) [RETICS-RD06/0026]
- Comunidad Autonoma de Madrid [SAL2006/0275]
- Agencia Lain Entralgo [NDG07/9]
- Fundacion C.I.E.N.
- Instituto Carlos III [85016/09]
- Spanish Ministry of Science and Innovation
- Fundacion Teofilo Hernando
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Galantamine is a drug currently used to treat Alzheimer's disease (AD); in this group of patients it has been observed that concomitant ischemic brain injury can accelerate their cognitive deficit. We have previously shown that galantamine can afford neuroprotection on in vitro and in vivo models related to brain ischemia. In this context, this study was planned to investigate the intracellular signaling pathways implicated in the protective effect of galantamine on an in vitro brain ischemia-reperfusion model, namely rat hippocampal slices subjected to oxygen and glucose deprivation (OGD) followed by reoxygenation. Galantamine protected hippocampal slices subjected to OGD in a concentration-dependent manner; at 15 mu M, cell death was reduced to almost control levels. The neuroprotective effects of galantamine were reverted by mecamylamine and AG490, but not by atropine, indicating that nicotinic receptors and Jak2 participated in this action. Galantamine also prevented p65 translocation into the nucleus induced by OGD; this effect was also linked to nicotinic receptors and Jak2. Furthermore, galantamine reduced iNOS induction and production of NO caused by OGD via Jak2. ROS production by NADPH oxidase (NOX) activation was also inhibited by galantamine. In conclusion, galantamine afforded neuroprotection under OGD-reoxygenation conditions by activating a signaling pathway that involves nicotinic receptors, Jak2 and the consequent inhibition of NOX and NF kappa B/iNOS. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. (C) 2011 Elsevier Ltd. All rights reserved.
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