期刊
PLOS ONE
卷 8, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0056586
关键词
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资金
- NHR Foundation
- Wenner-Gren Fellowship
- Soderberg's Foundation
- AFA Foundation
- Knut and Alice Wallenberg's Foundation
- Swedish Research Council
- LeDucq Foundation
- Swedish Brain Foundation
- Hallsten's Research Foundation
- Swedish Agency for Innovation Systems (VINNOVA)
- Swedish Cancer Foundation
- Swedish Stroke Foundation
- Royal Swedish Agency
- Magnus Bergwall's Foundation
- Karolinska Institute
Central nervous system (CNS) disorders such as ischemic stroke, multiple sclerosis (MS) or Alzheimers disease are characterized by the loss of blood-brain barrier (BBB) integrity. Here we demonstrate that the small tyrosine kinase inhibitor imatinib enhances BBB integrity in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). Treatment was accompanied by decreased CNS inflammation and demyelination and especially reduced T-cell recruitment. This was supported by downregulation of the chemokine receptor (CCR) 2 in CNS and lymph nodes, and by modulation of the peripheral immune response towards an anti-inflammatory phenotype. Interestingly, imatinib ameliorated neuroinflammation, even when the treatment was initiated after the clinical manifestation of the disease. We have previously shown that imatinib reduces BBB disruption and stroke volume after experimentally induced ischemic stroke by targeting platelet-derived growth factor receptor -alpha (PDGFR-alpha) signaling. Here we demonstrate that PDGFR-alpha signaling is a central regulator of BBB integrity during neuroinflammation and therefore imatinib should be considered as a potentially effective treatment for MS.
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