RETRACTED: Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke (Retracted article. See FEB, 2023)

被引:62
作者
Ottani, Alessandra [1 ]
Giuliani, Daniela [1 ]
Mioni, Chiara [1 ]
Galantucci, Maria [1 ]
Minutoli, Letteria [2 ]
Bitto, Alessandra [1 ,2 ]
Altavilla, Domenica [2 ]
Zaffe, Davide [3 ]
Botticelli, Annibale R. [4 ]
Squadrito, Francesco [2 ]
Guarini, Salvatore [1 ]
机构
[1] Univ Modena & Reggio Emilia, Pharmacol Sect, Dept Biomed Sci, I-41100 Modena, Italy
[2] Univ Messina, Pharmacol Sect, Dept Clin & Expt Med & Pharmacol, Messina, Italy
[3] Univ Modena & Reggio Emilia, Dept Anat & Histol, I-41100 Modena, Italy
[4] Univ Pavia, Dept Human Pathol, I-27100 Pavia, Italy
关键词
cerebral and systemic damage; ischemic stroke; melanocortins; nicotinic acetylcholine receptors; vagus nerve; MELANOCYTE-STIMULATING HORMONE; KAPPA-B ACTIVATION; INFLAMMATORY RESPONSE; HEMORRHAGIC-SHOCK; DELAYED TREATMENT; RAPID ACTIVATION; ARTERY-OCCLUSION; NEUROPROTECTION; ALPHA; INTERLEUKIN-6;
D O I
10.1038/jcbfm.2008.140
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A vagus nerve-mediated, efferent cholinergic protective pathway activated by melanocortins is operative in circulatory shock and myocardial ischemia. Moreover, melanocortins have neuroprotective effects against brain damage after ischemic stroke. Here we investigated cerebral and systemic pathophysiologic reactions to focal cerebral ischemia in rats induced by intrastriatal microinjection of endothelin-1, and the possible protective role of the melanocortin-activated vagal cholinergic pathway. In the striatum and liver of saline-treated control rats, the activation of extracellular signal-regulated kinases, c-jun N-terminal kinases, and caspase-3, the increase in tumor necrosis factor-alpha (TNF-alpha) concentration and DNA fragmentation, as well as the increase in TNF-a plasma levels, occurred 10 and 20 h after the ischemic insult suggesting an activation of inflammatory and apoptotic responses. Treatment with [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH; 3 or 9 h after stroke) suppressed the inflammatory and apoptotic cascades at central and peripheral level. Bilateral vagotomy and pharmacologic blockade of peripheral nicotinic acetylcholine receptors blunted the protective effect of NDP-alpha-MSH. The present results show that focal brain ischemia in rats causes significant effects not only in the brain, but also in the liver. Moreover, our data support the hypothesis that a protective, melanocortin-activated, vagal cholinergic pathway is likely operative in conditions of ischemic stroke.
引用
收藏
页码:512 / 523
页数:12
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