title: Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice.
abstract: OBJECTIVE
  Statins are widely used in the primary and secondary prevention of ischemic stroke, but their effects on stroke-induced immunodepression and poststroke infections are elusive. We investigated the effects of simvastatin treatment on stroke-induced splenic atrophy and lung susceptibility to bacterial infection in acute experimental stroke in mice.
  
  
  METHODS
  Ischemic stroke was induced by transient middle cerebral artery occlusion, followed by reperfusion. In some experiments, splenectomies were performed 2 weeks before middle cerebral artery occlusion. Animals were randomly assigned to sham and middle cerebral artery occlusion groups treated subcutaneously with vehicle or simvastatin (20 mg/kg per day). Brain infarction, neurological function, brain interferon-γ expression, splenic atrophy and apoptosis, and lung infection were examined.
  
  
  RESULTS
  Simvastatin reduced stroke-induced spleen atrophy and splenic apoptosis via increased mitochrondrial antiapoptotic Bcl-2 expression and decreased proapoptotic Bax translocation from cytosol into mitochondria. Splenectomy reduced brain interferon-γ (3 days) and infarct size (5 days) after stroke, and these effects were reversed by adoptive transfer of splenocytes. Simvastatin inhibited brain interferon-γ (3 days) and reduced infarct volume and neurological deficits (5 days) after stroke, and these protective effects were observed not only in naive stroke mice but also in splenectomied stroke mice adoptively transferred with splenocytes. Simvastatin also decreased the stroke-associated lung susceptibility to spontaneous bacterial infection.
  
  
  CONCLUSIONS
  Results provide the first direct experimental evidence that simvastatin ameliorates stroke-induced peripheral immunodepression by attenuating spleen atrophy and lung bacterial infection. These findings contribute to a better understanding of the beneficial effects of statins in the treatment of stroke.
authors: Vascular Biology and Stroke Research Laboratory, Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors: Rong
authors: R
authors: Jin
authors: Xiaolei
authors: X
authors: Zhu
authors: Lin
authors: L
authors: Liu
authors: Anil
authors: A
authors: Nanda
authors: D Neil
authors: DN
authors: Granger
authors: Guohong
authors: G
authors: Li
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D017209:Apoptosis; D001284:Atrophy / Q000628:therapy*; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism*; D020520:Brain Infarction; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007239:Infections; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D013156:Splenectomy; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007371:Interferon-gamma; D019821:Simvastatin
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