Quote:
Originally Posted by Ronhutton
http://www.onderzoekinformatie.nl/en...ek/OND1327711/
Project: Blood-brain barrier dysfunction in Parkinson's disease in vivo
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Titel Blood-brain barrier dysfunction in Parkinson's disease in vivo
Abstract Most cases of PD are sporadic and are known as idiopathic PD. Genetic susceptibility and exposure to neurotoxic substances are contributors to brain tissue malfunctioning and neuronal cell loss. Several pathogenic mechanisms have been discovered to contribute to the demise of these cells. Similarly, loss of blood-brain-barrier (BBB) function and neuro*inflammation have been postulated to be fac*tors in the cause and progression of neuro*degenerative diseases. In my thesis, I study different aspects of pathophysiology of Parkinson s disease using functional imaging with Positron Emission Tomography (PET). Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms. In Parkinson s disease, fluorodopa PET is used to measure the presynaptic dopaminergic defecit, mostly in the striatum, while glucose PET scans show striatal and cortical energy metabolism. I studied brain dopamine and glucose metabolism in PD patients with freezing of gait to investigate specific patterns of striatal and cortical defects underlying this symptom. Besides this, I study the role of possible pathogenetic mechanisms in PD neurodegeneration. BBB efflux function of the P-glycoprotein (P-gp) pump can be measured in vivo using radiolabeled verapamil and PET. Inflammation through activated microglia can be measured in vivo using PET and the radiolabeled isoquinolone PK11195, which is a ligand for the peripheral benzodiazepine receptor. I studied BBB P-gp function in PD patients in different disease stages and in patients with parkinsonism (PSP, MSA). Neuroinflammation will also be studies in PD patients in different disease stages. Furthermore, using the microPET scanner, P-gp function and neuroinflammation will be measured in the 6-OHDA animal model of PD dopaminergic degeneration, in which the effect of anti-inflammatory treatment using COX2-inhibitors will be studied.
Period 04/2004 - 11/2008
Dissertation Yes
URL http://www.rug.nl/bcn/research/phdPr...ts/bartelsanna
Related organisations
Secretariat: Graduate School for Behavioral and Cognitive Neurosciences - BCN (RuG)
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hello ron,
http://www.ebmonline.org/cgi/content/full/223/2/175
http://www.ebmonline.org/cgi/content/full/223/2/175
Zinc Deficiency Exacerbates Loss in Blood-Brain Barrier Integrity Induced by Hyperoxia Measured by Dynamic MRI
Michael D. Noseworthy* and Tammy M. Bray,1
* Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1; and
Department of Human Nutrition, The Ohio State University, Columbus, Ohio 43210–1295
Exposure of the brain to excessive oxidative stress increases the risk of neuronal disorders. Structurally, the brain is well protected. However, the brain is susceptible to oxidative damage due to regionally high concentrations of iron and ascorbate, a high content of polyunsaturated fatty acids, high oxygen consumption, and a relatively low antioxidant capacity (1). An antioxidant nutrient deficiency could further increase the susceptibility of the brain to oxidative stress.
Premature infants are at high risk to excessive oxidative stress. In addition to their developmental immaturity, these newborns frequently have low nutritional status and low antioxidant storage, including zinc (2). To enhance oxygen uptake they are placed into hyperoxic incubators. Elevated environmental oxygen has been shown to be deleterious to the lungs and eyes (3) of premature infants due to excess oxygen radical formation. These infants are also susceptible to a variety of neurological disorders, including cerebral palsy, and other motor and cognitive disorders (4, 5). The brain problems observed might be due, in part, to free radical damage similar to that observed in other tissues.
Disruption of the blood-brain barrier (BBB), a capillary ultrastructural formation that protects the brain (6), could be an initiating event in the etiology of some of the brain disorders observed in the premature infant. We speculate that low zinc status of premature infants could be an important variable exacerbating this brain oxidative damage since zinc acts as an antioxidant important in BBB membrane stability and in the protection of membrane protein thiol groups (7). Zinc is involved in brain phospholipid metabolism (8). Alteration of BBB integrity due to weakened antioxidant defenses and increased oxidative exposure may predispose the brain of premature infants to oxidative damage leading to neurological disorders. In addition, zinc also functions in the brain as a neuromodulator. It may be involved in the regulation of neurotransmission by modulating presynaptic neurotransmitter release.
It is difficult to avoid artifacts when one measures the oxidative damage in the brain ex vivo since the removed brain is subject to rapid biochemical changes and oxidation. Therefore, we chose to investigate the effects of zinc deficiency and hyperoxia on BBB integrity using dynamic MRI, which permits noninvasive monitoring of changes in the brain over time. To evaluate brain oxidative stress, results were compared to established biochemical indices that may indicate the presence or absence of imbalance in oxidative tone.