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Role of subconcussion in repetitive mild traumatic brain injury pt 2

Julian Bailes, MD, NorthShore Neurological Institute

This is a follow up to the wespeak program originally aired Febraury 25, 2014. Joining us is author and Neurosurgeon, Julian Bailes and Neuropsychologist, Mark Lovell. They will be highlighting the major points of the paper and will answer some additional questions regarding concussion in sports.

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Role of subconcussion in repetitive mild traumatic brain injury

Julian Bailes, MD, NorthShore Neurological Institute

This We-Speak On-Line Journal Club features Dr. Julian Bailes presenting his paper entitled, "Role of subconcussion in repetitive mild traumatic brain injury." Dr. Bailes is the Bennett Tarkington Chairman of the Department of Neurosurgery; Co-Director, NorthShore Neurological Institute, NorthShore University Health System and Clinical Professor of Neurosurgery at the University of Chicago Pritzker School of Medicine. Dr. Bailes is also the advisor to the NFL Players Association Committee on Head Injuries. Joining the discussion is an expert panel including: Dr. Mark Lovell--Chairman of the Board and Chief Scientific Officer at ImPact Applications and the co-creator of ImPact testing. Dr. Maggy Moore--Assistant Professor at Northern Michigan University. Dr. Bryan Dixon--Director of Sports Medicine at Marquette General Hospital and Medical Director of the United States Olympic Education Center. Please join us for this live and interactive discussion of head injury in sports.

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Microvesicles as mediators of tissue regeneration

Keith Sabin, MS, University of Minnesota

The use of stem cells in the treatment of various diseases and injuries has received increasing interest during the past decade. Injected stem cells, such as mesen- chymal stem cells, stimulate tissue repair largely through the secretion of soluble fac- tors that regulate various processes of tissue regeneration, including inflammatory responses, apoptosis, host cell proliferation, and angiogenesis. Recently, it has become apparent that stem cells also use membranous small vesicles, collectively called microvesicles, to repair damaged tissues. Microvesicles are released by many types of cells and exist in almost all types of body fluids. They serve as a vehicle to transfer protein, messenger RNA, and micro RNA to distant cells, altering the gene expression, proliferation, and differentiation of the recipient cells. Although animal models and in vitro studies have suggested promising applications for microvesicles-based regeneration therapy, its effectiveness and feasibility in clinical medicine remain to be established. Further studies of the basic mechanisms respon- sible for microvesicle-mediated tissue regeneration could lead to novel approaches in regenerative medicine.

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Neutrophil Degranulation and Immunosuppression

Trisha Sippel, PhD, University of Colorado

The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell–derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell–mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3z expression within peripheral blood from patients with GBM. Sorted CD11bþ cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients. Clin Cancer Res; 17(22); 6992–7002. !2011 AACR.

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Leptin promotes glioblastoma

John Lawrence, PhD, et al, Upper Michigan Brain Tumor Center

The hormone leptin has a variety of functions. Originally known for its role in satiety and weight loss, leptin more recently has been shown to augment tumor growth in a variety of cancers. Within gliomas, there is a correlation between tumor grade and tumor expression of leptin and its receptor. This suggests that autocrine signaling within the tumor microenvironment may promote the growth of high-grade gliomas. Leptin does this through stimulation of cellular pathways that are also advantageous for tumor growth and recurrence: antiapoptosis, proliferation, angiogenesis, and migration. Conversely, a loss of leptin expression attenuates tumor growth. In animal models of colon cancer and melanoma, a decline in the expression and secretion of leptin resulted in a reduction of tumor growth. In these models, positive mental stimulation through environmental enrichment decreased leptin secretion and improved tumor outcome. This review explores the link between leptin and glioblastoma.

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