Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia.
OBJECTIVE
Bacterial pneumonia is the most common cause of death in patients sustaining acute stroke and is believed to result from an increased aspiration. Recently, stroke-induced immunodeficiency was described in a mouse model of cerebral ischemia, which is primarily caused by overactivation of sympathetic nervous system. We tested if stroke-induced immunodeficiency increases the risk of pneumonia after aspiration in a newly developed model of poststroke pneumonia.


METHODS
Experimental stroke in mice was induced by occlusion of the middle cerebral artery (MCAO) for 60 minutes. Aspiration pneumonia was induced by intranasal application of 20 microL of a defined suspension of Streptococcus pneumoniae in phosphate-buffered saline 4 or 14 days after MCAO. Treatment comprised moxifloxacin (100 mg/kg body weight, six times every 2 hours after operation) or propranolol (30 mg/kg body weight, immediately before as well as 4 and 8 hours after MCAO). Readout was lung histology and bacterial counts in lung and blood.


RESULTS
Nasal inoculation of only 200 colony-forming units of S. pneumoniae caused severe pneumonia and bacteremia after experimental stroke, whereas 200,000 colony-forming units are needed to induce comparable disease in sham animals. Aspiration pneumonia in stroke animals outlasted acute stroke state but was preventable by beta-adrenoreceptor blockade.


CONCLUSIONS
Experimental stroke propagates bacterial aspiration from harmless intranasal colonization to harmful pneumonia. Prevention of infections by beta-adrenoreceptor blockade suggests that immunodepression by sympathetic hyperactivity is essential for progression of bacterial aspiration to pneumonia.
Prass
Konstantin
K
Department of Experimental Neurology, Charité Universitaetsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Braun
Johann S
JS
Dirnagl
Ulrich
U
Meisel
Christian
C
Meisel
Andreas
A
D000208:Acute Disease; D000281:Administration, Intranasal; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D016470:Bacteremia / Q000209:etiology; D002395:Catecholamines / Q000502:physiology; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000276:immunology; D001239:Inhalation; D008297:Male; D051379:Mice; D009296:Nasal Cavity / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000209:etiology*; D011018:Pneumonia, Pneumococcal / Q000209:etiology; D013047:Specific Pathogen-Free Organisms; D013296:Streptococcus pneumoniae; D020521:Stroke / Q000150:complications* / Q000276:immunology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines