Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral, and anal sphincter function in a dog model. Part 3. nicotinic receptor characterization.

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined.

Mechanisms involved in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox)-derived reactive oxygen species (ROS) modulation of muscle function in human and dog bladders.

Roles of redox signaling in bladder function is still under investigation. We explored the physiological role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) in regulating bladder function in humans and dogs. Mucosa-denuded bladder smooth muscle strips obtained from 7 human organ donors and 4 normal dogs were mounted in muscle baths, and trains of electrical field stimulation (EFS) applied for 20 minutes at 90-second intervals.

Restoring bladder function using motor and sensory nerve transfers: a cadaveric feasibility study.

Objective: Bladder dysfunction after nerve injury has a variable presentation, and extent of injury determines whether the bladder is spastic or atonic. The authors have proposed a series of 3 nerve transfers for functional innervation of the detrusor muscle and external urethral sphincter, along with sensory innervation to the genital dermatome. These transfers are applicable to only cases with low spinal segment injuries (sacral nerve root function is lost) and largely preserved lumbar function.

Dog and human bladders have different neurogenic and nicotinic responses in inner versus outer detrusor muscle layers.

The aim of this study was to investigate layer and species variations in detrusor muscle strip responses to myogenic, neurogenic, and nicotinic, and muscarinic receptor stimulations. Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips were mounted in muscle baths and maximal responses to neurogenic stimulation using electrical field stimulation (EFS) and myogenic stimulation using potassium chloride (KCl, 120 mM) determined.

Lateralization of bladder function in normal female canines.

This study aimed to identify potential lateralization of bladder function. Electrical stimulation of spinal roots or the pelvic nerve's anterior vesical branch was performed bilaterally in female dogs. The percent difference between the left and right stimulation-induced increased detrusor pressure was determined.

Identification of the NADPH Oxidase (Nox) Subtype and the Source of Superoxide Production in the Micturition Centre.

Oxidative inflammatory damage to specialised brain centres may lead to dysfunction of their associated peripheral organs, such as the bladder. However, the source of reactive oxygen species (ROS) in specific brain regions that regulate bladder function is poorly understood. Of all ROS-generating enzymes, the NADPH oxidase (Nox) family produces ROS as its sole function and offers an advantage over other enzymes as a drug-targetable molecule to selectively control excessive ROS.

SARS-CoV-2 BNT162b2 vaccine-induced humoral response and reactogenicity in individuals with prior COVID-19 disease.

BACKGROUNDMost individuals with prior COVID-19 disease manifest long-term protective immune responses against reinfection. Accordingly, we tested the hypothesis that humoral immune and reactogenicity responses to a SARS-CoV-2 mRNA vaccine differ in individuals with and without prior COVID-19 disease.METHODSHealth care workers (n = 61) with (n = 30) and without (n = 31) prior COVID-19 disease received two 30 μg doses of Pfizer BNT162b2 vaccine 3 weeks apart.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 1: attenuation of purinergic bladder smooth muscle contractions.

This study determined the effect of pelvic organ decentralization and reinnervation 1 yr later on the contribution of muscarinic and purinergic receptors to ex vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, 8 were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 mo later.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions.

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later.

TRPV4 receptor as a functional sensory molecule in bladder urothelium: Stretch-independent, tissue-specific actions and pathological implications.

The newly recognized sensory role of bladder urothelium has generated intense interest in identifying its novel sensory molecules. Sensory receptor TRPV4 may serve such function. However, specific and physiologically relevant tissue actions of TRPV4, stretch-independent responses, and underlying mechanisms are unknown and its role in human conditions has not been examined.

Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2.

Bladder dysfunction is associated with the overexpression of the intermediate filament (IF) proteins desmin and vimentin in obstructed bladder smooth muscle (BSM). However, the mechanisms by which these proteins contribute to BSM dysfunction are not known. Previous studies have shown that desmin and vimentin directly participate in signal transduction.

Fully implantable neural recording and stimulation interfaces: Peripheral nerve interface applications.

Background: Peripheral nerve interfacing has many applications ranging from investigation of neural signals to therapeutic intervention for varied diseases. This need has driven technological advancements in the field of electrode arrays and wireless systems for in-vivo electrophysiological experiments. Hence we present our fully implantable, programmable miniaturized wireless stimulation and recording devices.

Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra.

Aims: We sought to determine whether somatic lumbar nerve transfer to the pelvic nerve's anterior vesical branch after sacral decentralization for detrusor muscle reinnervation also leads to aberrant innervation of the bladder outlet.

Methods: Twenty-six female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots (ie, sacral decentralization). Immediately afterward, 12 received genitofemoral nerve transfer and 9 received femoral nerve branch transfer.

Nerve transfer for restoration of lower motor neuron-lesioned bladder and urethra function: establishment of a canine model and interim pilot study results.

Objective: Previous patient surveys have shown that patients with spinal cord or cauda equina injuries prioritize recovery of bladder function. The authors sought to determine if nerve transfer after long-term decentralization restores bladder and sphincter function in canines.

Methods: Twenty-four female canines were included in this study.

Acute bladder decentralization in hound dogs: Preliminary results of effects on hypogastric nerve electroneurograms and detrusor pressure responses to spinal root and hypogastric nerve stimulation.

Objective: We aimed to refine electroneurogram techniques for monitoring hypogastric nerve activity during bladder filling, and then examined nerve activity in normal intact versus acutely decentralized bladders.

Methods: Effects of electrical stimulation of hypogastric nerves or lumbar ventral roots on detrusor pressure were examined, as were effects of isoflurane versus propofol anesthetics on hypogastric nerve stimulation evoked pressure. Hypogastric nerve activity was then recorded using custom-made bipolar cuff electrodes during bladder filling before and after its transection between the spinal cord and electrode to eliminate efferent nerve signals.

Determining integrity of bladder innervation and smooth muscle function 1 year after lower spinal root transection in canines.

Aims: To assess bladder smooth muscle function and innervation after long-term lower spinal root transection in canines.

Methods: Thirteen female mixed-breed hound dogs underwent bladder decentralization, which included transection of all sacral dorsal and ventral roots caudal to L7 and hypogastric nerves, bilaterally (n = 3); all sacral roots and hypogastric nerves plus transection of L7 dorsal roots, bilaterally (n = 4); or a sham operation (n = 6). At a year after initial surgery, bladder function was assessed in vivo by stimulation of the pelvic plexus.

Clarification of the Innervation of the Bladder, External Urethral Sphincter and Clitoris: A Neuronal Tracing Study in Female Mongrel Hound Dogs.

Many studies examining the innervation of genitourinary structures focus on either afferent or efferent inputs, or on only one structure of the system. We aimed to clarify innervation of the bladder, external urethral sphincter (EUS) and clitoris. Retrograde dyes were injected into each end organ in female dogs.

Lumbar to sacral root rerouting to restore bladder function in a feline spinal cord injury model: Urodynamic and retrograde nerve tracing results from a pilot study.

Aims: Lumbar to sacral rerouting surgery can potentially allow voiding via a skin-central nervous system-bladder reflex pathway. Here, we assessed if this surgery was effective in treating neurogenic bladder dysfunction/sphincter in felines.

Methods: Eight cats underwent spinal cord transection (SCT) at thoracic level 10/11.

Evidence of vagus nerve sprouting to innervate the urinary bladder and clitoris in a canine model of lower motoneuron lesioned bladder.

Aims: Complete spinal cord injury does not block perceptual responses or inferior solitary nucleus activation after genital self-stimulation, even though the vagus is not thought to innervate pelvic structures. We tested if vagus nerve endings sprout after bladder decentralization to innervate genitourinary structures in canines with decentralized bladders.

Methods: Four reinnervation surgeries were performed in female hounds: bilateral genitofemoral nerve transfer to pelvic nerve with vesicostomy (GNF-V) or without (GFN-NV); and left femoral nerve transfer (FNT-V and FNT-NV).

Endocannabinoids and the Digestive Tract and Bladder in Health and Disease.

Components of the so-called endocannabinoid system, i.e., cannabinoid receptors, endocannabinoids, as well as enzymes involved in endocannabinoid synthesis and degradation, have been identified both in the gastrointestinal and in the urinary tract.

Neural reconstruction methods of restoring bladder function.

During the past century, diverse studies have focused on the development of surgical strategies to restore function of a decentralized bladder after spinal cord or spinal root injury via repair of the original roots or by transferring new axonal sources. The techniques included end-to-end sacral root repairs, transfer of roots from other spinal segments to sacral roots, transfer of intercostal nerves to sacral roots, transfer of various somatic nerves to the pelvic or pudendal nerve, direct reinnervation of the detrusor muscle, or creation of an artificial reflex pathway between the skin and the bladder via the central nervous system. All of these surgical techniques have demonstrated specific strengths and limitations.

Neuromuscular nicotinic receptors mediate bladder contractions following bladder reinnervation with somatic to autonomic nerve transfer after decentralization by spinal root transection.

Purpose: We investigated whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway.

Materials And Methods: After decentralizing the bladder by transecting the sacral roots in dogs we performed peripheral nerve transfer, including bilateral genitofemoral to pelvic nerve transfer and unilateral left femoral nerve to bilateral pelvic nerve transfer. Reinnervation was assessed 7.

Alterations in nerve-evoked bladder contractions in a coronavirus-induced mouse model of multiple sclerosis.

Background: Patients with neurodegenerative diseases such as multiple sclerosis, Parkinson's, and Alzheimer's often present with lower urinary tract symptoms (LUTS, urinary frequency, urgency, nocturia and retention) resulting from damage to the peripheral and central nervous systems. These studies were designed to examine the changes in the function of the bladder that may underlie neurogenic bladder dysfunction using a mouse model of demyelination in the CNS.

Methods: Bladders from 12 week old male C57BL/6J mice with coronavirus-induced encephalomyelitis (CIE, a chronic, progressive demyelinating disease model of human MS), and age-matched controls, were cut into 5-7 strips and suspended in physiological muscle baths for tension measurement in response to agonists and electric field stimulation (EFS).