Cholinergic anti-inflammatory pathway in intracerebral hemorrhage

• Published in: Brain research 2010-01, Vol.1309, p.164-171
• Main Authors: Lee, Soon-Tae, Chu, Kon, Jung, Keun-Hwa, Kang, Kyung-Mook, Kim, Jin-Hee, Bahn, Jae-Joon, Jeon, Daejong, Kim, Manho, Lee, Sang Kun, Roh, Jae-Kyu
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Animals; Arrhythmias, Cardiac - chemically induced; Arrhythmias, Cardiac - physiopathology; Biological and medical sciences; Brain Edema - drug therapy; Brain Edema - etiology; Brain Edema - physiopathology; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - metabolism; Cerebral Hemorrhage - physiopathology; Cholinergic anti-inflammatory pathway; Collagenases; Encephalitis - drug therapy; Encephalitis - metabolism; Encephalitis - physiopathology; High mobility group box 1; Inflammation Mediators - metabolism; Injections, Intraventricular; Intracerebral hemorrhage; Male; Medical sciences; Muscarine - pharmacology; Muscarine - therapeutic use; Muscarinic Agonists - pharmacology; Muscarinic Agonists - therapeutic use; Neurology; Rats; Rats, Sprague-Dawley; Spleen - drug effects; Spleen - innervation; Spleen - physiology; Tumor necrosis factor-alpha; Vagus nerve; Vagus Nerve - drug effects; Vagus Nerve - physiology; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.10.076

Abstract Stimulated vagus nerve excretes acetylcholine into the peripheral immune organs such as the spleen, reducing innate inflammation. Here, we investigated whether activation of this “cholinergic anti-inflammatory pathway” can be used to reduce cerebral inflammation in a model of hemorrhagic stroke. Experimental intracerebral hemorrhage (ICH) was induced by stereotaxic collagenase injection in rats. Muscarine, an activator of the vagus nerve, or phosphate-buffered saline (control) was injected into the lateral ventricle after induction of ICH. Intraventricular muscarine injection increased heart rate variability in the ICH model, suggesting increased vagus nerve output. Muscarine-injected ICH rats showed improved neurologic outcomes, reduced brain water content, and decreased levels of inflammatory mediators in both brain and spleen. Central muscarine injection was ineffective at reducing cerebral edema without spleen, suggesting that the effect of muscarine is mediated through the vagus nerve-spleen pathway rather than through a direct interaction with the brain. Our results suggest that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself.