Published Online
on August 31, 2006

A more recent version of this article appeared on October 1, 2006

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Submitted on March 20, 2006
Revised on June 22, 2006
Accepted on July 6, 2006

Stroke Propagates Bacterial Aspiration to Pneumonia in a Model of Cerebral Ischemia

Konstantin Prass MD; Johann S. Braun MD; Ulrich Dirnagl MD; Christian Meisel MD; and Andreas Meisel MD^*

From the Departments of Experimental Neurology (K.P., J.S.B., U.D., A.M.) and Medical Immunology (C.M.), Charité Universitaetsmedizin, Berlin, Germany.

^* To whom correspondence should be addressed. E-mail: andreas.meisel{at}charite.de.

Background and Purpose--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 µL 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 -adrenoreceptor blockade.

Conclusions--Experimental stroke propagates bacterial aspiration from harmless intranasal colonization to harmful pneumonia. Prevention of infections by -adrenoreceptor blockade suggests that immunodepression by sympathetic hyperactivity is essential for progression of bacterial aspiration to pneumonia.

Key words: aspiration • mice • pneumonia • Streptococcus pneumoniae • stroke

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