“…6 | ANTIFIBROSIS STRATEGIES 6.1 | Bladder wall fibrosis and OAB symptoms Many bladder pathologies that demonstrate OAB symptoms also show the replacement of detrusor smooth muscle with connective tissue (fibrosis) that consists of collagens and elastin embedded in a ground substance of proteoglycans. 49 This apparently counterintuitive observation may be explained in several ways: ECM is generally stiffer than muscle tissue so that bladder wall compliance is reduced, with sensory thresholds achieved at lower filling volumes; detrusor spontaneous contractions arise when nerve-mediated responses are suppressed 50 ; and the increased density of collagenproducing cells, such as myofibroblasts and interstitial cells, themselves generate irregular propagating electrical signals. 51 The reduction of ECM deposition will, therefore, be a useful target to restore normal bladder function.…”
Aims. To review evidence for novel drug targets that can manage overactive bladder symptoms. Methods. A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterise their use to treat overactive bladder. Results. Five classes of agents or cellular pathways were considered. 1) Cyclic nucleotide-dependent (cAMP and cGMP) pathways that modulate ATP release from motor nerves and urothelium. 2) Novel targets for beta-3 agonists, including the bladder wall vasculature and muscularis mucosa. 3) Several TRP channels (TRPV1, TRPV4, TRPA1, TRPM4) and their modulators in affecting detrusor overactivity. 4) small conductance Ca 2+activated K + channels and their influence on spontaneous contractions. 5) antifibrosis agents that act to modulate directly or indirectly the TGF-beta pathway-the canonical fibrosis pathway. Conclusions. Specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above potential agents are distributed among most organ systems. The tasks are to determine: more detail of the pathological changes that occur in the overactive bladder and; how specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.
“…6 | ANTIFIBROSIS STRATEGIES 6.1 | Bladder wall fibrosis and OAB symptoms Many bladder pathologies that demonstrate OAB symptoms also show the replacement of detrusor smooth muscle with connective tissue (fibrosis) that consists of collagens and elastin embedded in a ground substance of proteoglycans. 49 This apparently counterintuitive observation may be explained in several ways: ECM is generally stiffer than muscle tissue so that bladder wall compliance is reduced, with sensory thresholds achieved at lower filling volumes; detrusor spontaneous contractions arise when nerve-mediated responses are suppressed 50 ; and the increased density of collagenproducing cells, such as myofibroblasts and interstitial cells, themselves generate irregular propagating electrical signals. 51 The reduction of ECM deposition will, therefore, be a useful target to restore normal bladder function.…”
Aims. To review evidence for novel drug targets that can manage overactive bladder symptoms. Methods. A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterise their use to treat overactive bladder. Results. Five classes of agents or cellular pathways were considered. 1) Cyclic nucleotide-dependent (cAMP and cGMP) pathways that modulate ATP release from motor nerves and urothelium. 2) Novel targets for beta-3 agonists, including the bladder wall vasculature and muscularis mucosa. 3) Several TRP channels (TRPV1, TRPV4, TRPA1, TRPM4) and their modulators in affecting detrusor overactivity. 4) small conductance Ca 2+activated K + channels and their influence on spontaneous contractions. 5) antifibrosis agents that act to modulate directly or indirectly the TGF-beta pathway-the canonical fibrosis pathway. Conclusions. Specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above potential agents are distributed among most organ systems. The tasks are to determine: more detail of the pathological changes that occur in the overactive bladder and; how specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.
“…It has protective and sensory functions, and its spontaneous activity is closely related to the detrusor. 6 Therefore, these characteristics of the bladder should be taken into account in any repair or reconstruction of the bladder.Figure 1.Bladder anatomy and process of bladder hemi section. (a) The bladder wall consists of four layers: mucosa (urothelium), the innermost layer facing the bladder cavity; Submucosal connective tissue layer (fixed layer), muscle layer and serosa layer covering the outer surface.…”
The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.
“…Due to the large size of the porcine bladder, the investigations were limited to the UB trigone (UBT), which is important for the continence and prevention of vesicoureteral reflux, and the high concentration of the intramural nerve elements (Andersson, 2002; Pidsudko, 2004; Pradidarcheep et al, 2011; for review, see Fry & McCloskey, 2019).…”
The present study investigated the influence of castration performed at neonatal age on neuronal elements in the intramural ganglia of the urinary bladder trigone (UBT) in male pigs using double‐labeling immunohistochemistry. The ganglia were examined in intact (IP) 7‐day‐old (castration day) pigs, and at 3 and 6 months after surgery. In IP and control (3‐ and 6‐month‐old noncastrated pigs) groups, virtually, all neurons were adrenergic (68%) or cholinergic (32%) in nature. Many of them (32%, 51%, and 81%, respectively; 56%, 75%, and 85% adrenergic; and 32%, 52%, and 65% cholinergic, respectively) stained for the androgen receptor (AR), and only a small number of nerve cells were caspase‐3 (CASP‐3)‐positive. In 3‐ and 6‐month‐old castrated pigs, an excessive loss (87.6% and 87.5%, respectively) of neurons and intraganglionic nerve fibers was observed. The majority of the surviving adrenergic (61% and 72%, respectively) and many cholinergic (41% and 31%, respectively) neurons expressed CASP‐3 and were also AR‐positive (61% and 66%, and 40% and 36%, respectively). This study revealed for the first time the excessive loss of intramural UBT neurons following castration, which could have resulted from apoptosis induced by androgen deprivation.
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