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

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Secretariat: Graduate School for Behavioral and Cognitive Neurosciences - BCN (RuG)