Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation

Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Spain.
Neuropharmacology (Impact Factor: 5.11). 11/2011; 62(2):1082-90. DOI: 10.1016/j.neuropharm.2011.10.022
Source: PubMed


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 μM, 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 NFκB/iNOS. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

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Available from: Maria Dolores Martin-de-Saavedra, Feb 07, 2015
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    • "NADPH oxidase (NOX) is one of the main contributors to such excessive ROS production. Another contributor to ROS generation is nitric oxide (NO), generated by inducible NO synthetase (iNOS) (Egea et al., 2012). Stopping the ischemic cascade by targeting its components is one potential strategy for acute stroke treatment, known as the neuroprotection strategy. "
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