TY - JOUR
T1 - Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice
AU - Jin, Rong
AU - Zhu, Xiaolei
AU - Liu, Lin
AU - Nanda, Anil
AU - Granger, D. Neil
AU - Li, Guohong
PY - 2013/4
Y1 - 2013/4
N2 - Background and Purpose-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.
AB - Background and Purpose-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.
UR - http://www.scopus.com/inward/record.url?scp=84876205383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876205383&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.111.000633
DO - 10.1161/STROKEAHA.111.000633
M3 - Article
C2 - 23391769
AN - SCOPUS:84876205383
SN - 0039-2499
VL - 44
SP - 1135
EP - 1143
JO - Stroke
JF - Stroke
IS - 4
ER -