Imatinib treatment reduces brain injury in a murine model of traumatic brain injury

Enming Joseph Su, Linda Teresa Fredriksson, Mia Kanzawa, Shannon Moore, Erika Folestad, Tamara K Stevenson, Ingrid Nilsson, Maithili Sashindranath, Gerald P Schielke, Mark Warnock, Margaret Ragsdale, Kris M Mann, Anna-Lisa E Lawrence, Robert Lindsay Medcalf, Ulf Eriksson, Geoffrey G Murphy, Daniel A Lawrence

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24 Citations (Scopus)

Abstract

Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor a (PDGFRa) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRa, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRa.
Original languageEnglish
Pages (from-to)1 - 12
Number of pages12
JournalFrontiers in Cellular Neuroscience
Volume9
Issue number(Art. No: 385)
DOIs
Publication statusPublished - 2015

Cite this

Su, E. J., Fredriksson, L. T., Kanzawa, M., Moore, S., Folestad, E., Stevenson, T. K., Nilsson, I., Sashindranath, M., Schielke, G. P., Warnock, M., Ragsdale, M., Mann, K. M., Lawrence, A-L. E., Medcalf, R. L., Eriksson, U., Murphy, G. G., & Lawrence, D. A. (2015). Imatinib treatment reduces brain injury in a murine model of traumatic brain injury. Frontiers in Cellular Neuroscience, 9((Art. No: 385)), 1 - 12. https://doi.org/10.3389/fncel.2015.00385