Functional NeuroUrology

PI:
Dr. G. van Koeveringe, Assoc.Prof., MD, PhD
Prof. Ph. van Kerrebroeck

Postdocs:   
Dr. C. Meriaux, PhD
Dr. M.S. Rahnama’i, PhD

PhD-students:
J. Drossaerts MSc
R. Hohnen MSc
K. Rademakers MSc
A. Schueth MSc
D. Vrijens MSc

Focus of research:
NeuroUrology: bladder signalling, control mechanisms and neuro-modulation

The research focus is directed towards fundamental understanding of bladder and lower urinary tract physiology, pharmacology and the origins and treatment of lower urinary tract dysfunction. Three project lines are ongoing in order to study different levels of bladder dysfunction in a translational research program based in the Research School for Mental health and Neuroscience and in close collaboration with the clinical urology department and the Pelvic Care Centre Maastricht.

Line 1:
Characterisation, analysis and physiological and structural mapping of control pathways within the urinary bladder wall and their connections with the central nervous system. In this basic research line, multiple pharmacological pathways have been studied in the intrinsic control mechanism inside the bladder wall, involving the network of interstitial cells and autonomous bladder activity.  This part of the research is performed in collaboration with M. van Zandvoort (dept of Genetics and Cell biology).  The way by which this mechanism is efferently modulated or afferently used by the central nervous system is subject to future electrophysiological recording and tracer studies. In a collaborative project with the Neurosurgery department (Y. Temel) connections of the lower urinary tract to specific brainstem areas such as PAG and dorsal raphe are being studied. Furthermore the assessment of the control pathways, by means of for example analysis of the non-voiding detrusor activity is expanded to animal models representing different mechanisms of diseases affecting bladder control such as a guinea pig hyperdistention underactive bladder model and an Alzheimer transgenic mouse model (behavioural studies in association with the Neuro-psychology group of J.Prickaerts). The determination of the respective contribution of either bladder or brain/nerve dysfunction to these diseases will contribute to a better understanding of the clinical problems and (patho)physiological mechanisms. Moreover knowledge of these systems is necessary to understand and improve current treatment regimens such as:  neurostimulation, neuromodulation and both peripheral and central pharmacological therapy.  These activities are currently being funded by an EU FP7-ITN Marie Curie grant and partly by the Astellas Europe fund Prize 2012.

Line 2:
The bladder control system in humans in the normal and the diseased state. A relationship of an existing overactive bladder syndrome with non-voiding activity is studied using high-resolution urodynamic measurements in order to develop a physiological biomarker. This part of the study was funded by the “Astellas exploratory non-voiding activity study” via CTCM. A relationship is sought between psychological profile and the degree of bladder fullness perception. Related to this new research areas are being explored in collaboration with the Pelvic care center Maastricht and the department of Psychiatry with the focus on associations of functional bladder and pelvic floor complaints in combination with psychiatric comorbidity.   For the underactive bladder, an algorithm for detection diagnosis and evaluation is being developed using patient databases from Hannover and from the Pelvic care center Maastricht,  in a collaborative project with the university of Hannover (M. Oelke)  In a retranslational way, a link is made with line 1 in which an underactive bladder model is developed using acute and chronic hyperdistention.  This research is funded by the Astellas Europe fund.

Line 3:
Neuromodulation in humans for complaints of overactive bladder and voiding dysfunction (over- and underactive bladder and bladder outlet), supervised by Prof.dr. Ph. Van Kerrebroeck and co-supervised by Dr. G. A. van Koeveringe. In this research line both working mechanisms (using techniques and models described above) and an optimisation of the current neuromodulation treatments by means of determination of predictive factors and optimisation of techniques are the main subjects to be studied. Patient selection through for example determination of certain psychological patient traits (in collaboration with C. Leue, dept of Psychiatry), sub-characterisation of the diseases and evaluation of the largest urological neuromodulation patient cohort will be done using different possible psychological, physiological, biochemical and imaging biomarkers.