Microcirculatory aspects of neurogenic bladder syndrome

Járomi, Péter
Microcirculatory aspects of neurogenic bladder syndrome.
[Thesis]

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Abstract in foreign language

The microcirculatory aspects of inflammatory disorders are of importance in the pathology of the urinary system. Our first aim was to perform a comparative analysis of the microcirculatory responses of the urinary bladder in infectious and non-infectious inflammatory animal models with direct or indirect endothelial damage. To this end, we compared the local microcirculatory consequences of experimental interstitial (IC) cystitis and hemorrhagic cystitis (HC) with those of bladder ischemia/reperfusion (IR). We found that not only IR, where direct endothelial damage is present, but also HC and IC, where microcirculatory inflammatory reactions are secondary after urothelial and interstitial damage, are associated with manifest polymorphonuclear leukocyte (PMN)–endothelial cell interactions. This finding confirms the common role of PMN-mediated microcirculatory reactions in the pathogenesis of bladder diseases. The overexpression of transient receptor potential vanilloid type 1 (TRPV1) has been demonstrated in IC cases as well as in cases of neurogenic bladder. In addition, TRPV1 agonists have also previously been used during pharmacological management of these diseases. Therefore, our next aim was to examine the microcirculatory effects of local capsaicin treatment (the archetypical TRPV1 agonist). In our study, capsaicin induced rapid increases in PMN leukocyte rolling and adhesion and in adhesion molecule expression in the postcapillary venules of the urinary bladder, which was prevented by neonatal sensory chemodenervation with capsaicin and competitive TRPV1 antagonism. The effect of specific receptor antagonist therapy showed that TRPV1-induced calcitonin gene-related peptide (CGRP) release initiates the PMN–endothelial cell interaction by promoting leukocyte rolling, but adhesion is influenced by both CGRP and substance P. Our final goal is to implement medical research in clinical practice. Depending on the underlying cause, neurogenic bladder can manifest in both overactive and underactive forms. Diagnosis and treatment of both manifestations of neurogenic bladder remain a challenge in urology practice because disease severity cannot easily be assessed and the most common symptoms are non-specific. For this reason, our last aim was to provide an algorithm that aims to facilitate rapid and efficient diagnosis and assessment of disease severity. This may also aid in decision making on the potential pharmacological and invasive therapeutic approaches to protecting the upper urinary tract by maintaining low pressure values in the bladder.

Item Type: Thesis (PhD)
Creators: Járomi, Péter
Hungarian title label: A neurogén hólyag szindróma mikrokeringésének szempontjai
Subjects: 03. Medical and health sciences > 03.02. Clinical medicine > 03.02.20. Urology and nephrology > 03.02.20.02. Urology
Divisions: Doctoral School of Multidisciplinary Medical Sciences
Discipline label: Medicine > Theoretical Medicine
Language label: English
Defence date label: 2020. December 07.
Uncontrolled Keywords: Húgyhólyag, mikrokeringés, leukocyta, neurogén hólyag, TRPV1, interstitialis cystitis, haemorrhagias cystitis
Item ID: 10710
MTMT id: 31956271
doi: https://doi.org/10.14232/phd.10710
Date Deposited: 2020. Nov . 18. 15:33
Last Modified: 2021. Nov . 05. 12:46
URI: https://doktori.bibl.u-szeged.hu/id/eprint/10710
Defence/Citable status: Defended.

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