Publications by authors named "William C De Groat"

Article Synopsis
  • The study investigated how sex affects lower urinary tract function in mice with and without spinal cord injury (SCI), focusing on the roles of certain molecular mechanisms.
  • Results showed that female mice voided differently than male mice, with females experiencing relaxation and males exhibiting bursting activity during urination.
  • Both sexes showed an increase in specific molecular markers (Piezo2, TRPV1, and NGF) related to nerve function and bladder health after SCI, but there were no significant differences in these levels between male and female mice following the injury.
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Aims: To determine the role of opioid and β-adrenergic receptors in bladder underactivity induced by prolonged pudendal nerve stimulation (PNS).

Methods: In α-chloralose anesthetized cats, 30-min PNS was applied repeatedly for 3-9 times to induce poststimulation or persistent bladder underactivity. Then, naloxone (opioid receptor antagonist, 1 mg/kg, IV) or propranolol (β-adrenergic receptor antagonist, 3 mg/kg, IV) was given to reverse the bladder underactivity.

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Article Synopsis
  • - The article discusses recent findings on lower urinary tract dysfunction (LUTD) caused by spinal cord injury (SCI) above the sacral level, using animal models to understand the impact on micturition control and neurophysiology.
  • - LUTD results from disrupted neural circuits that impair the coordination between the bladder and urethral sphincters, leading to issues such as involuntary voiding and ineffective bladder emptying after SCI.
  • - Key mechanisms behind SCI-induced LUTD include hyperexcitability of bladder afferents, with different pathways contributing to conditions like detrusor overactivity during storage and detrusor sphincter dyssynergia during voiding.
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Objective: The purpose of this study is to determine whether adaptively stepwise increasing the intensity of a high-frequency (10 kHz) biphasic stimulation (HFBS) can produce nerve conduction block without generating a large initial response.

Materials And Methods: In anesthetized cats, three cuff electrodes were implanted on the left pudendal nerve for stimulation or block. The urethral pressure increase induced by pudendal nerve stimulation was used to measure the pudendal nerve block induced by HFBS.

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Aims: Nerve growth factor (NGF) has been implicated as a key molecule of pathology-induced changes in C-fiber afferent nerve excitability, which contributes to the emergence of neurogenic detrusor overactivity due to spinal cord injury (SCI). It is also known that the second messenger signaling pathways activated by NGF utilize p38 Mitogen-Activated Protein Kinase (MAPK). We examined the roles of p38 MAPK on electrophysiological properties of capsaicin sensitive bladder afferent neurons with SCI mice.

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Objective: To determine the role of ion concentrations and ion pump activity in conduction block of myelinated axon induced by a long-duration direct current (DC).

Methods: A new axonal conduction model for myelinated axons based on the classical Frankenhaeuser-Huxley (FH) equations is developed that includes ion pump activity and allows the intracellular and extracellular Na and K concentrations to change with axonal activity.

Results: Action potential generation, propagation, and acute DC block occurring within a short period (milliseconds) that do not significantly change the ion concentrations or trigger ion pump activity are successfully simulated by the new model in a similar way as the classical FH model.

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The purpose of this study was to determine how sensory neurons respond to high-frequency membrane potential alternation between depolarization and hyperpolarization. Membrane currents were recorded from dissociated dorsal root ganglion (DRG) neurons of adult rats using the whole cell patch clamp technique in voltage clamp mode. Stepwise depolarization of the membrane was applied first to determine the threshold membrane potential for inducing an action potential (AP) current.

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This review article aims to summarize the recent advancement in basic research on lower urinary tract dysfunction (LUTD) following spinal cord injury (SCI) above the sacral level. We particularly focused on the neurophysiologic mechanisms controlling the lower urinary tract (LUT) function and the SCI-induced changes in micturition control in animal models of SCI. The LUT has two main functions, the storage and voiding of urine, that are regulated by a complex neural control system.

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Objective: This study aimed at determining whether stimulation of sacral spinal roots can induce penile erection in cats.

Materials And Methods: In anesthetized cats, a 20-gauge catheter was inserted into the corpus cavernosum to measure the penile pressure. Stimulus pulses (5-80 Hz, 0.

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A new axonal conduction model was used to analyze the interaction between intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency (kHz) biphasic stimulation (HFBS).The model includes intracellular and extracellular sodium and potassium concentrations and ion pumps. First, the HFBS (1 kHz, 5.

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This study examined the effect of sacral neuromodulation on persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PudNS). In 10 α-chloralose-anesthetized cats, repetitive application of 30-min PudNS induced bladder underactivity evident as an increase in bladder capacity during a cystometrogram (CMG). S1 or S2 dorsal root stimulation (15 or 30 Hz) at 1 or 1.

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Objectives: This study aims to determine temperature effect on nerve conduction block induced by high-frequency (kHz) biphasic stimulation (HFBS).

Materials And Methods: Frog sciatic nerve-muscle preparation was immersed in Ringer's solution at a temperature of 15 or 20 °C. To induce muscle contractions, a bipolar cuff electrode delivered low-frequency (0.

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The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can improve nonobstructive urinary retention (NOUR) induced by prolonged pudendal nerve stimulation (PNS). In this exploratory acute study using eight cats under anesthesia, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS.

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The aim of this study was to determine whether stimulation of sacral spinal nerve roots can induce defecation in cats. In anesthetized cats, bipolar hook electrodes were placed on the S1-S3 dorsal and/or ventral roots. Stimulus pulses (1-50 Hz, 0.

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The purpose of this modeling study is to develop a novel method to block nerve conduction by high frequency biphasic stimulation (HFBS) without generating initial action potentials. An axonal conduction model including both ion concentrations and membrane ion pumps is used to analyze the axonal response to 1 kHz HFBS. The intensity of HFBS is increased in multiple steps while maintaining the intensity at a sub-threshold level to avoid generating an action potential.

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Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, Bar and Bar, that have different functions and target different spinal circuitry. Both types of neurons project to the L-S spinal intermediolateral (IML) nucleus, whereas Bar neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals.

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The goal of this study is to induce low-pressure voiding by stimulation and bilateral 1 kHz post-stimulation block of the pudendal nerves. In anesthetized cats, wire hook electrodes were placed on the left and/or right pudendal nerves. Stimulus pulses (30 Hz, 0.

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Objective: To reveal the possible mechanisms underlying poststimulation block induced by high-frequency biphasic stimulation (HFBS).

Materials And Methods: A new axonal conduction model is developed for unmyelinated axons. This new model is different from the classical axonal conduction model by including both ion concentrations and membrane ion pumps to allow analysis of axonal responses to long-duration stimulation.

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Article Synopsis
  • The study investigates how TRP channels (specifically TRPA1, TRPV1, and TRPC) in guinea pig urinary bladders affect bladder function by releasing neurotransmitters.
  • Agonists like AITC, CAPS, and OA-NO were tested, revealing that AITC significantly increased bladder contractions, an effect that could be influenced by certain antagonists and inhibitors.
  • Findings suggest that there are at least two types of afferent nerves in the guinea pig bladder: Type A (TRPA1 receptors) which stimulate contractions, and Type B (TRPV1, TRPA1, TRPC receptors) which can inhibit them through CGRP release.
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Spinal neuronal mechanisms regulate recovered involuntary micturition after spinal cord injury (SCI). It was recently discovered that dopamine (DA) is synthesized in the rat injured spinal cord and is involved in lower urinary tract (LUT) activity. To fully understand the role of spinal DAergic machinery in micturition, we examined urodynamic responses in female rats during pharmacological modulation of the DA pathway.

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The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS.

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Article Synopsis
  • * A study tested an implantable pudendal nerve stimulator (PNS) on four cats with complete SCI, successfully improving bladder management by inducing efficient voiding and promoting urine storage.
  • * The PNS worked by stimulating the pudendal nerve, allowing for low pressure and high-efficiency voiding, demonstrating potential for developing similar treatments for humans with SCI.
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Objective: To reveal the possible contribution of changes in membrane ion concentration gradients and ion pump activity to axonal conduction/block induced by long-duration electrical stimulation.

Methods: A new model for conduction and block of unmyelinated axons based on the classical Hodgkin-Huxley (HH) equations is developed to include changes in Na and K concentrations and ion pumps. The effect of long-duration stimulation on axonal conduction/block is analyzed by computer simulation using this new model.

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Benign prostatic hyperplasia (BPH) is an age-related debilitating prostatic disease that is frequently associated with prostatic inflammation and bothersome lower urinary tract symptoms (LUTS). Animal models have shown that formalin- and bacterial-induced prostatic inflammation can induce bladder dysfunction; however, the underlying mechanisms contributing to prostatic inflammation in BPH and bladder dysfunction are not clear. We previously reported that E-cadherin expression in BPH is downregulated in hyperplastic nodules compared with expression in adjacent normal tissues.

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The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve.

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