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Trans-NIH Angiogenesis Workshop; May 20-21, 2013
  • Abstracts

    The Brain-Bone Marrow Connection: Dysfunction in Diabetes

    Maria Grant, MD  [ View bio ]
    (University of Florida)

    Despite decades of investigation that have implicated endothelial dysfunction, inflammation, and oxidative stress in diabetes-induced vascular pathophysiology, the precise sequence of cellular and molecular events that initiate and establish vascular disease in individuals with diabetes remains poorly defined. Dysfunctional brain-bone marrow communication may play a key role in this pathophysiology and promote microvascular complications. Stressors such as hyperglycemia increase the expression of the chemokine (C-C motif) ligand 2 (CCL2) and microglia activation in the paraventricular nucleus of the hypothalamus (PVN). These PVN changes trigger an increase in PVN preautonomic neuronal activity to the rostral ventrolateral medulla (RVLM) and increase sympathetic neuronal activity (SNA) to the bone marrow. Enhanced SNA acutely promotes mobilization of inflammatory mononuclear cells into the circulation, followed by extravasation of these cells into the PVN (responding to the increased CCL2) and leading to sustained neuroinflammation. Later, due to this sympathetic hyperactivity, neuropathy affecting the bone marrow develops and results in changes in hematopoiesis that lead to generation of increased proinflammatory monocytes and reduced numbers of vascular progenitor cells. These changes lead to reduced vascular repair and promote development of microvascular complications, including diabetic retinopathy. Recently, we demonstrated that targeting central nervous system (CNS) inflammation with an agent such as minocycline that crosses the blood-brain barrier can correct microglia activation in the CNS and help correct diabetes-associated changes in the bone marrow, restoring vascular repair and reducing inflammation leading to prevention of retinopathy, nephropathy, and neuropathy and improving wound healing.

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Workshop Organizer: NIH

NCI:Nancy Emenaker, PhD, RD
Suzanne Forry-Schaudies, PhD
NHLBI:Yunling Gao, MD, PhD
NIDDK: Teresa Jones, MD

NIH - National Institutes of Health: Turning Discovery Into Health

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