Nerve growth factor release from the urothelium increases via activation of bladder C‐fiber in rats with cerebral infarction

Yokokawa, Ryusei; Akino, Hironobu; Ito, Hiroki; Zha, Xinmin; Yokoyama, Osamu

doi:10.1002/nau.23142

Cited by 8 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KPR-5714 dose-dependently increased the mean voided volume and decreased voiding frequency without affecting total voided volume (Table 2). Yokokawa et al (2017) revealed that bladder C-fibers are activated by cerebral infarction, and C-fiber afferent nerves play an important role on the secretion of nerve growth factor; thus, we supposed that the improvement of the voiding behavior by KPR-5714 may be also mediated via inhibition of bladder C-fiber hyperactivity similar to the case of acetic acid instillation.…”

Section: Discussionmentioning

confidence: 83%

KPR-5714, a Novel Transient Receptor Potential Melastatin 8 Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats

Nakanishi

Fujimori

Aizawa

et al. 2020

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Transient receptor potential (TRP) melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (Ad-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized ), a novel and selective TRPM8 antagonist, to assess its therapeutic potential against frequent urination in rat models with overactive bladder (OAB). In calcium influx assays with HEK293T cells transiently expressing various TRP channels, KPR-5714 showed a potent TRPM8 antagonistic effect and high selectivity against other TRP channels. Intravenously administered KPR-5714 inhibited the hyperactivity of mechanosensitive C-fibers of bladder afferents and dose-dependently increased the intercontraction interval shortened by intravesical instillation of acetic acid in anesthetized rats. Furthermore, we examined the effects of KPR-5714 on voiding behavior in conscious rats with cerebral infarction and in those exposed to cold in metabolic cage experiments. Cerebral infarction and cold exposure induced a significant decrease in the mean voided volume and increase in voiding frequency in rats. Orally administered KPR-5714 dose-dependently increased the mean voided volume and decreased voiding frequency without affecting total voided volume in these models. This study demonstrates that KPR-5714 improves OAB in three different models by inhibiting exaggerated activity of mechanosensitive bladder C-fibers and suggests that KPR-5714 may provide a new and useful approach to the treatment of OAB. SIGNIFICANCE STATEMENTTRPM8 is involved in bladder sensory transduction and plays a role in the abnormal activation in hypersensitive bladder disorders. KPR-5714, as a novel and selective TRPM8 antagonist, may provide a useful treatment for the disorders related to the hyperactivity of bladder afferent nerves, particularly in overactive bladder.

show abstract

Section: Discussionmentioning

confidence: 83%

KPR-5714, a Novel Transient Receptor Potential Melastatin 8 Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats

Nakanishi

Fujimori

Aizawa

et al. 2020

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…NGF is released in the inflammatory status and can modulate the expression of the P2X3 receptor. In addition, activation of the bladder C-fiber owing to various etiologies induces the release of NGF from the urothelium [40]. The findings of the current study suggested that NGF and associated purinergic signaling molecules were involved in BPAO-induced bladder overactivity.…”

Section: Discussionmentioning

confidence: 53%

Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia

Chiang

Liao

Mao

et al. 2021

IJMS

View full text Add to dashboard Cite

(1) Background: We established a new bladder ischemia rat model through bilateral partial iliac arterial occlusion (BPAO) and investigated the therapeutic effect of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs); (2) Methods: The study included four groups: (1) sham, (2) BPAO, (3) BPAO + ADSCs, and (4) BPAO + ADSC-derived MVs. Female Wistar rats with BPAO were injected with ADSCs or ADSC-derived MVs through the femoral artery. Doppler flowmetry and real-time laser speckle contrast imaging were performed to quantify blood flow in the common iliac arteries and bladder microcirculation. A 24-h behavior study and transcystometrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxidation assay were performed. The expressions of P2X2, P2X3, M2, and M3 receptors and nerve growth factor (NGF) were evaluated; (3) Results: BPAO significantly reduced bladder microcirculation, intercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding contraction, neutrophil infiltration, and malondialdehyde and NGF levels. ADSCs and ADSC-derived MVs significantly ameliorated these effects. The results of Western blot showed that the BPAO group exhibited the highest expression of M3 and P2X2 receptors. ADSCs significantly attenuated the expressions of M2 and P2X2 receptors. ADSC-derived MVs significantly attenuated the expressions of M3 and P2X2 receptors; (4) Conclusions: ADSCs and ADSC-derived MVs ameliorated the adverse effects of BPAO including bladder overactivity, bladder ischemia, and oxidative stress. Inflammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism.

show abstract

“…Nerve growth factor (NGF) is a protein primarily responsible for the differentiation and survival of neurons in the peripheral nervous system [ 4 ], so NGF has been one of neuroprotective agents for treating cerebral infarction [ 5 – 7 ] and ischemic brain [ 8 , 9 ]. The situation of focus recovery was observed and evaluated after cerebral infarction treated by NGF and other neuroprotective agents, which needed more reliable objective indicators.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of nerve growth factor on canine cerebral infarction evaluated by MRI

et al. 2017

View full text Add to dashboard Cite

To explore therapeutic effect of nerve growth factor (NGF) on cerebral infarction by establishing canine middle cerebral artery occlusion (MCAO) infarct model. The magnetic resonance imaging (MRI) technology was used to study effects of NGF on cerebral infarction, and the results of MRI indexes (such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI)) were compared with the results of pathology, cell biology and molecular biology. The clinical manifestations of the canine infarction model treated by NGF were significantly improved within 7 days compared with control group. The therapeutic evaluation of NGF effect could be determine by canine cerebral infarction treated by NGF within 6 hours according to DWI and PWI. From 6 hours to 7 days, therapeutic evaluation of NGF could be determine by T1WI, T2WI and FLAIR. DWI and PWI could find the change of cerebral ischemia at the early stage, provide advantages for qualitative diagnosis of early-stage cerebral infarction and observation of efficacy in early treatment, initially showing that their great potential for NGF role on cerebral ischemia and mechanism.

show abstract

Nerve growth factor release from the urothelium increases via activation of bladder C‐fiber in rats with cerebral infarction

Cited by 8 publications

References 27 publications

KPR-5714, a Novel Transient Receptor Potential Melastatin 8 Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats

KPR-5714, a Novel Transient Receptor Potential Melastatin 8 Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats

Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia

Therapeutic effect of nerve growth factor on canine cerebral infarction evaluated by MRI

Contact Info

Product

Resources

About