Title

 

Authors

A. Bitto¹, D. Altavilla¹, N. Irrera¹, S. Guarini², D. Giuliani², F. Squadrito¹.

¹Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
²Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.

 

Abstract

The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. The effect of glucocorticoids and other humoral mediators on inflammatory responses has been studied extensively in the past decades. In contrast, neural control of inflammation has only been recently described. Stimulated vagus nerve excretes acetylcholine into the peripheral immune organs such as the spleen, reducing innate inflammation. Autonomic regulation of local and systemic inflammation through the 'cholinergic anti-inflammatory pathway', a mechanism consisting of the vagus nerve and its major neurotransmitter, acetylcholine, a process dependent on the nicotinic acetylcholine receptor alpha7 (nAChRalpha7) subunit. Stimulation of the nAChRalpha7 by nicotine or acetylcholine initiates neural inhibition of inflammation, this pathway was initially discovered in animal models of endotoxemia and septic shock, and later described in a number of other diseases. The activation of the so called "cholinergic anti-inflammatory pathway" has been used to reduce cerebral inflammation in different models of brain damage, such as: ischemic and hemorrhagic stroke; and traumatic brain injury. Melanocortin peptides have been shown to activate the cholinergic anti-inflammatory pathway and have been proved successful for the treatment of the above mentioned brain injury conditions. The results obtained in these studies demonstrate a neuroprotective mechanisms of vagal nerve stimulation.