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Biddeford, ME, United States

The blood-brain barrier (BBB) is the regulated interface that mediates selective transcellular transport of nutrients and essential components from the blood into the brain parenchyma. Many neurodegenerative diseases including stroke, multiple sclerosis, rheumatoid arthritis, and AIDS dementia exhibit loss of BBB integrity. Despite the increasing body of evidence for the involvement of glia in maintaining the BBB, few studies have addressed glial/endothelial/extracellular matrix interactions. A chemically induced astrocyte lesion provides a noninvasive model to study reversible BBB dysfunction in vivo. Blood-brain barrier integrity was assessed with fluorescent dextran tracers (3-70 kDa) and magnetic resonance imaging, in parallel with confocal and electron microscopy imaging of the neurovascular unit. These studies demonstrated modified tight-junction protein expression with loss of vascular integrity. We propose that adherens junction proteins and extracellular matrix remodeling provide a temporary size-selective barrier, whereas astrocyte and microglia activation direct tight-junction proteins to paracellular domains and restore BBB integrity. Morphological comparisons were made with the area postrema, a circumventricular organ with a naturally porous BBB. Further studies into cellular mechanisms of glial/endothelial/extracellular matrix interactions may identify novel glial-based therapeutic targets and innovate therapies for modulating diseases in which gliosis and raised levels of pro-inflammatory mediators are central components. Source

PURPOSE:: To evaluate the ability of optical coherence tomography angiography to detect early microvascular changes in eyes of diabetic individuals without clinical retinopathy. METHODS:: Prospective observational study of 61 eyes of 39 patients with diabetes mellitus and 28 control eyes of 22 age-matched healthy subjects that received imaging using optical coherence tomography angiography between August 2014 and March 2015. Eyes with concomitant retinal, optic nerve, and vitreoretinal interface diseases and/or poor-quality images were excluded. Foveal avascular zone size and irregularity, vessel beading and tortuosity, capillary nonperfusion, and microaneurysm were evaluated. RESULTS:: Foveal avascular zone size measured 0.348 mm (0.1085–0.671) in diabetic eyes and 0.288 mm (0.07–0.434) in control eyes (P = 0.04). Foveal avascular zone remodeling was seen more often in diabetic than control eyes (36% and 11%, respectively; P = 0.01). Capillary nonperfusion was noted in 21% of diabetic eyes and 4% of control eyes (P = 0.03). Microaneurysms and venous beading were noted in less than 10% of both diabetic and control eyes. Both diabetic and healthy control eyes demonstrated tortuous vessels in 21% and 25% of eyes, respectively. CONCLUSION:: Optical coherence tomography angiography was able to image foveal microvascular changes that were not detected by clinical examination in diabetic eyes. Changes to the foveal avascular zone and capillary nonperfusion were more prevalent in diabetic eyes, whereas vessel tortuosity was observed with a similar frequency in normal and diabetic eyes. Optical coherence tomography angiography may be able to detect diabetic eyes at risk of developing retinopathy and to screen for diabetes quickly and noninvasively before the systemic diagnosis is made. © 2015 by Ophthalmic Communications Society, Inc. Source

Bonini Filho M.A.,University of New England at Biddeford

PURPOSE:: To describe the retinal microvasculature of the eyes with nonarteritic retinal artery occlusion (RAO) based on optical coherence tomography angiography. METHODS:: Cross-sectional, prospective, observational study performed from September 2014 through February 2015. En face projection of optical coherence tomography angiography images centered at the macula and optic disk of the eyes presenting with RAO were acquired using the RTVue XR Avanti with AngioVue software. Qualitative analysis of the morphology of the superficial and deep retinal capillary plexuses, and radial peripapillary capillaries was performed. Retinal vasculature images using optical coherence tomography angiography were correlated with fluorescein angiography images. RESULTS:: Seven patients (seven eyes) were enrolled in the study, including three eyes with central RAO and four eyes with branch RAO. Distinct differences in the distribution of zones of decreased vascular perfusion between the superficial and deep retinal capillary plexus corresponding to areas of delayed dye perfusion on fluorescein angiography were demonstrated in 6 of 7 (86.5%) eyes. CONCLUSION:: This small series suggests that optical coherence tomography angiography imaging can accurately discern retinal capillary plexuses at different levels in the eyes with RAO and may be sensitive for more precisely characterizing the extent of macular ischemia and monitoring vascular flow changes during the course of the disease. © 2015 by Ophthalmic Communications Society, Inc. Source

Willis C.L.,University of New England at Biddeford
Methods in Molecular Biology

The goal of this chapter is to highlight methods used to demonstrate in vivo changes in astrocyte expression at the blood-brain barrier (BBB). Loss of BBB integrity is seen in many acute and chronic disease conditions. However, despite the importance of the BBB to homeostasis and correct functioning of the CNS, the nature of factors responsible for the induction and maintenance of BBB properties in development and the adult remains unclear. We have studied the role of astrocytes in modulating BBB integrity in two in vivo models using a gliotoxin (3-chloropropanediol), and under hypoxic stress. 3-chloropropanediol- induced astrocytic loss within the inferior colliculus leads to loss of endothelial tight junction protein expression and loss of BBB integrity. As glial fibrillary acidic protein (GFAP)-immunopositive astrocytes repopulated the lesion, tight junction protein expression returned to paracellular domains and BBB integrity was restored. Under hypoxic conditions, increased GFAP expression was seen with changes in tight junction protein expression and loss of BBB integrity. These studies suggest a critical role for glial/endothelial interactions in regulating BBB integrity in health and disease. © 2012 Springer Science+Business Media, LLC. Source

Pardue K.T.,University of New England at Biddeford
Nurse Educator

The growing emphasis on teamwork and care coordination within health care delivery is sparking interest in interprofessional education (IPE) among nursing and health profession faculty. Faculty often lack firsthand IPE experience, which hinders pedagogical reform. This article proposes a theoretically grounded framework for the design, implementation, and evaluation of IPE. Supporting literature and practical advice are interwoven. The proposed framework guides faculty in the successful creation and evaluation of collaborative learning experiences. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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