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Su EJ, Fredriksson L, Kanzawa M, et al. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury. Front Cell Neurosci. 2015;9:385doi: 10.3389/fncel.2015.00385.
Su, E. J., Fredriksson, L., Kanzawa, M., Moore, S., Folestad, E., Stevenson, T. K., Nilsson, I., Sashindranath, M., Schielke, G. P., Warnock, M., Ragsdale, M., Mann, K., Lawrence, A. L., 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, 9385. https://doi.org/10.3389/fncel.2015.00385
Su, Enming J, et al. "Imatinib treatment reduces brain injury in a murine model of traumatic brain injury." Frontiers in cellular neuroscience vol. 9 (2015): 385. doi: https://doi.org/10.3389/fncel.2015.00385
Su EJ, Fredriksson L, Kanzawa M, Moore S, Folestad E, Stevenson TK, Nilsson I, Sashindranath M, Schielke GP, Warnock M, Ragsdale M, Mann K, Lawrence AL, Medcalf RL, Eriksson U, Murphy GG, Lawrence DA. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury. Front Cell Neurosci. 2015 Oct 07;9:385. doi: 10.3389/fncel.2015.00385. eCollection 2015. PMID: 26500491; PMCID: PMC4596067.
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Front Cell Neurosci. 2015 Oct 07;9:385. doi: 10.3389/fncel.2015.00385. eCollection 2015.

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

Frontiers in cellular neuroscience

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

Affiliations

  1. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School Ann Arbor, MI, USA.
  2. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School Ann Arbor, MI, USA ; Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet Stockholm, Sweden.
  3. Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School Ann Arbor, MI, USA.
  4. Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet Stockholm, Sweden.
  5. Department of Molecular and Integrative Physiology, University of Michigan Medical School Ann Arbor, MI, USA.
  6. Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Monash University Melbourne, VIC, Australia.
  7. Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School Ann Arbor, MI, USA ; Department of Molecular and Integrative Physiology, University of Michigan Medical School Ann Arbor, MI, USA.
  8. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School Ann Arbor, MI, USA ; Department of Molecular and Integrative Physiology, University of Michigan Medical School Ann Arbor, MI, USA.

PMID: 26500491 PMCID: PMC4596067 DOI: 10.3389/fncel.2015.00385

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 α (PDGFRα) 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 PDGFRα, 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 PDGFRα.

Keywords: Imatinib; Morris water maze; TBI outcome; blood brain barrier; cerebral edema; platelet derived growth factor receptor α; platelet derived growth factor-CC; traumatic brain injury

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