Resveratrol preconditioning induces cellular stress proteins and is mediated via NMDA and estrogen receptors

• Published in: Neuroscience Vol. 166; no. 2; pp. 445 - 454
• Main Authors: Saleh, M.C, Connell, B.J, Saleh, T.M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 17-03-2010; Elsevier
• Subjects: Analysis of Variance; Animals; Antioxidants - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Blotting, Western; Brain - drug effects; Brain - metabolism; Brain - pathology; endoplasmic reticulum; Fundamental and applied biological sciences. Psychology; Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - metabolism; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; ischemia; Male; Medical sciences; Membrane Proteins - metabolism; middle cerebral artery occlusion; Molecular Chaperones - metabolism; Neurology; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Estrogen - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; renal sympathetic nerve activity; Stilbenes - pharmacology; Sympathetic Nervous System - metabolism; Time Factors; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; CPP; heart rate; TTC; GRP; HSP; (±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; 2,3,5-triphenol tetrazolium chloride; mean arterial pressure; HR; heat shock protein; MCA; N-methyl- d-aspartic acid; ER; middle cerebral artery; ischemia; RSNA; glucose-regulated protein; NMDA; MAP; endoplasmic reticulum; middle cerebral artery occlusion; renal sympathetic nerve activity; Sympathetic nerve; Estrogen receptor; Nervous system diseases; Cardiovascular disease; Glutamate receptor; Protein; Stress; Cerebral disorder; Vascular disease; Polyphenol; Central nervous system disease; Resveratrol; Brain ischemia; Proanthocyanidin; NMDA receptor; Preconditioning; Endoplasmic reticulum; Cerebrovascular disease; Renal nerve
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.12.060

Abstract Resveratrol pretreatment has been shown to provide neuroprotection in models of cerebral ischemia. This phenomenon, commonly termed preconditioning, promotes ischemic tolerance and may involve mild activation of endoplasmic reticulum stress pathways in the affected tissue. Systemic injection of resveratrol (2×10−3 , 2×10−4 , 1×10−4 mg/kg) 30 min prior to a 4 h period of right middle cerebral artery occlusion significantly reduced infarct area in the insular region of rat prefrontal cortex. This affect was blocked when resveratrol treatment was combined with a non-selective estrogen receptor antagonist, or preceded by intracortical injection of an NMDA receptor antagonist. The neuroprotective effect of resveratrol was associated with reduced renal sympathetic nerve activity as well as induction of resident endoplasmic reticulum chaperone proteins, glucose-regulated proteins 78 and 94. The calcium-sensitive chaperone heat shock protein 70 and the cysteine protease m calpain did not respond to resveratrol pretreatment. However, a significant induction of heat shock protein 70 was observed in the contralateral cortex of resveratrol pretreated rats following 4 h of right middle cerebral artery occlusion. These data suggest that resveratrol preconditioning promotes ischemic tolerance in the short term, in part via effects mediated through activation of estrogen and NMDA receptors, as well as through mild activation of cellular stress proteins.