Cholinergic anti-inflammatory pathway in intracerebral hemorrhage.
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.
Lee
Soon-Tae
ST
Stroke and Stem cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Chu
Kon
K
Jung
Keun-Hwa
KH
Kang
Kyung-Mook
KM
Kim
Jin-Hee
JH
Bahn
Jae-Joon
JJ
Jeon
Daejong
D
Kim
Manho
M
Lee
Sang Kun
SK
Roh
Jae-Kyu
JK
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D017364:Collagenases; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009116:Muscarine / Q000494:pharmacology* / Q000627:therapeutic use; D018721:Muscarinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D018836:Inflammation Mediators; D018721:Muscarinic Agonists; D009116:Muscarine; D017364:Collagenases; D000109:Acetylcholine