Study Title:

Ghrelin Turns Off Inflammation in Vagus Nerve

Study Abstract

The pathogenesis of stroke involves inflammation, apoptosis, and excitotoxicity, which is mediated in part by neuronal NO synthase (nNOS) activation. Ghrelin, an endogenous 28-amino acid peptide, is shown to exert antiapoptotic and anti-inflammatory properties. However, the effect of ghrelin in permanent focal cerebral ischemia and the role of the vagus nerve in its action remain unknown. To study this, male adult Sprague-Dawley rats underwent right-sided permanent middle cerebral artery occlusion (MCAO) with or without prior bilateral truncal vagotomy. This was followed by infusion of 4 nmol human ghrelin as treatment or saline as vehicle. Neurological deficit was assessed at 24 h after MCAO. Rats were killed thereafter, and brains were rapidly removed and analyzed for infarct size, markers of inflammation, excitotoxicity, and apoptosis. Compared with vehicle treatment, human ghrelin treatment in vagus nerve-intact rats after MCAO showed marked reduction in neurological deficit by 57% and infarct size by 25%. Middle cerebral artery occlusion resulted in increases in cerebral TNF-α, IL-6, neutrophil trafficking, matrix metalloproteinase 9 and nNOS gene expression, nitrotyrosine, and apoptosis. Human ghrelin treatment in vagus nerve-intact rats significantly decreased the above measurements. Human ghrelin treatment also improved 7-day survival and significantly decreased neurological deficit over the entire 7 days after MCAO in vagus nerve-intact rats compared with vehicle. Prior vagotomy, however, blunted human ghrelin's neuroprotective effects on neurological deficit, infarct size, TNF-α, neutrophil trafficking, nitrotyrosine, and apoptosis. Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway.

Study Information

Ghrelin suppresses inflammation and neuronal nitric oxide synthase in focal cerebral ischemia via the vagus nerve.

2011 March

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