Influenza virus infection aggravates stroke outcome.
Stroke
; 42(3): 783-91, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-21293018
ABSTRACT
BACKGROUND AND PURPOSE:
Stroke is triggered by several risk factors, including influenza and other respiratory tract infections. However, it is unknown how and in which way influenza infection affects stroke outcome.METHODS:
We infected mice intranasally with human influenza A (H1N1) virus and occluded the middle cerebral artery to induce ischemic strokes. Infarct volume and intracerebral hemorrhage were determined by histology. To evaluate the integrity of the blood-brain barrier and inflammation, we measured various cytokines in vivo and in vitro and performed immunohistochemistry of leukocyte markers, collagen IV, immunoglobulins, and matrix metalloproteinase-9.RESULTS:
Influenza virus infection increased infarct size. Whereas changes in cardiovascular parameters did not explain this effect, we found evidence for an inflammatory mechanism. In influenza virus infection, the respiratory tract released cytokines into the blood, such as RANTES that induced macrophage inflammatory protein-2 and other inflammatory mediators in the ischemic brain. In infected mice, there was an increased number of neutrophils expressing the matrix metalloproteinase-9 in the ischemic brain. This was accompanied by severe disruption of the blood-brain barrier and an increased rate of intracerebral hemorrhages after tissue plasminogen activator treatment. To investigate the role of cytokines, we blocked cytokine release by using GTS-21, a selective agonist of the α7 nicotinic acetylcholine receptor. GTS-21 ameliorated ischemic brain damage and improved survival.CONCLUSIONS:
Influenza virus infection triggers a cytokine cascade that aggravates ischemic brain damage and increases the risk of intracerebral hemorrhage after tissue plasminogen activator treatment. Blockade of cytokine production by α7 nicotinic acetylcholine receptor agonists is a novel therapeutic option to treat stroke in a proinflammatory context.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Acidente Vascular Cerebral
/
Influenza Humana
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Vírus da Influenza A Subtipo H1N1
Tipo de estudo:
Clinical_trials
/
Etiology_studies
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Risk_factors_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Stroke
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha