Neuroimmune-vascular cells and their pathological disorders Editorial Kirk J. Mantione Neuroscience Research Institute, State University of New York Old Westbury, Old Westbury, NY, USA Submitted: 12 October 2011 Accepted: 19 October 2011 Arch Med Sci 2011; 7, 5: 741-743 DOI: 10.5114/aoms.2011.25545 Copyright © 2011 Termedia & Banach The initiation and persistence of multiple organ pathologies, which may occur during life, are intimately associated with acute and chronic dysregulatory metabolic processes. Multiple organ pathologies may also be functionally associated with initiating traumatic events leading to a chronic state of proinflammatory cellular insults with resultant prolonged debilitation and negative quality of life. Along these lines, a large body of preclinical and clinical literature has established that acute and chronic perturbations of the functional coupling of vascular endothelial, immune, and neural cell types represent major contributory factors to the initiation and persistence of pathological states [1]. Furthermore, metabolic rundown in each of these cell types is intimately linked to primary functional deficits in their endosymbiont mitochondria. Mechanistically, dysregulation of mitochondrial respiration leads to impairment of intermediary energy metabolism, ATP production, and insufficient buffering of harmful reactive oxygen species [2]. Resultant damage to mtDNA has profound effects on mitochondrial rescue and biogenesis upon physiological demand. Similar criteria may relate to the elucidation of key cellular mechanisms underlying normal and premature ageing. In light of the above, common regulatory events and their potential dysregulation in neuroimmune-vascular disorders are listed below. Endothelia serve as major cellular conduits mediating oxygen and carbon dioxide exchange, nutrient transport, and autonomic tone in the peripheral and CNS vasculature. Notably, functional deficiencies in vascular endothelia has been documented in variety of human metabolic disorders including diabetes and cardiovascular disease [3-19]. Mitochondria- associated oxidative stress has been proposed as a major contributing factor to the severity of endothelial malfunction in these same metabolic disorders [3-19]. The immune system serves to defend the body from external and internal threats and keep multiple organ systems in metabolic homeostasis. Ongoing host-defense mechanisms utilize complementary regulatory processes to perform existential functions ranging from antibody production to immune surveillance and phagocytosis. Functional immunodeficiencies including perturbations in neuroimmune and vascular endothelial cellular coupling has been observed in multiple human pathological disorders [1, 20-34]. It has also become apparent that dysregulation of mitochondrial function mediated by disruption of constitutive nitric oxide signaling mechanisms represents a strong Corresponding author: Kirk J. Mantione PhD Neuroscience Research Institute State University of New York Old Westbury Old Westbury, NY11568, USA E-mail: kjmantione@sunynri.org