Challenges and opportunities of acquiring cortical recordings for chronic adaptive deep brain stimulation.

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex.

Implantation accuracy of novel polyimide stereotactic electroencephalographic depth electrodes-a human cadaveric study.

Introduction: Stereoelectroencephalography (sEEG) is a minimally invasive procedure that uses depth electrodes stereotactically implanted into brain structures to map the origin and propagation of seizures in epileptic patients. Implantation accuracy of sEEG electrodes plays a critical role in the safety and efficacy of the procedure. This study used human cadaver heads, simulating clinical practice, to evaluate (1) neurosurgeon's ability to implant a new thin-film polyimide sEEG electrode according to the instructions for use (IFU), and (2) implantation accuracy.

Stress-Induced Changes in Trophic Factor Expression in the Rodent Urinary Bladder: Possible Links With Angiogenesis.

Purpose: Substantive evidence supports a role of chronic stress in the development, maintenance, and even enhancement of functional bladder disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Increased urinary frequency and bladder hyperalgesia have been reported in rodents exposed to a chronic stress paradigm. Here, we utilized a water avoidance stress (WAS) model in rodents to investigate the effect of chronic stress on vascular perfusion and angiogenesis.

Electrochemical Testing of a New Polyimide Thin Film Electrode for Stimulation, Recording, and Monitoring of Brain Activity.

Subdural electrode arrays are used for monitoring cortical activity and functional brain mapping in patients with seizures. Until recently, the only commercially available arrays were silicone-based, whose thickness and lack of conformability could impact their performance. We designed, characterized, manufactured, and obtained FDA clearance for 29-day clinical use (510(k) K192764) of a new thin-film polyimide-based electrode array.

Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium.

Purpose: Lower urinary tract symptoms are known to significantly increase with age, negatively impacting quality of life and self-reliance. The urothelium fulfills crucial tasks, serving as a barrier protecting the underlying bladder tissue from the harsh chemical composition of urine, and exhibits signaling properties via the release of mediators within the bladder wall that affect bladder functioning. Aging is associated with detrimental changes in cellular health, in part by increasing oxidative stress in the bladder mucosa, and more specifically the urothelium.

First Food and Drug Administration Cleared Thin-Film Electrode for Intracranial Stimulation, Recording, and Monitoring of Brain Activity-Part 1: Biocompatibility Testing.

Subdural strip and grid invasive electroencephalography electrodes are routinely used for surgical evaluation of patients with drug-resistant epilepsy (DRE). Although these electrodes have been in the United States market for decades (first FDA clearance 1985), their fabrication, materials, and properties have hardly changed. Existing commercially available electrodes are made of silicone, are thick (>0.

Portable eye-tracking as a reliable assessment of oculomotor, cognitive and reaction time function: Normative data for 18-45 year old.

Eye movements measured by high precision eye-tracking technology represent a sensitive, objective, and non-invasive method to probe functional neural pathways. Oculomotor tests (e.g.

Normative data for ages 18-45 for ocular motor and vestibular testing using eye tracking.

Objective: Eye tracking technology has been employed in assessing ocular motor and vestibular function following vestibular and neurologic conditions, including traumatic brain injury (TBI). Assessments include tests that provide visual and motion (rotation) stimuli while recording horizontal, vertical, and torsional eye movements. While some of these tests have shown diagnostic promise in previous studies, their use in clinical practice is limited by the lack of normative data.

Acute spinal cord injury is associated with mitochondrial dysfunction in mouse urothelium.

Aim: To characterize the effects of acute spinal cord injury (SCI) on mitochondrial morphology and function in bladder urothelium and to test the therapeutic efficacy of early treatment with the mitochondrially targeted antioxidant, MitoTempo.

Methods: We used a mouse model of acute SCI by spinal cord transection between the T8-T9 vertebrae with or without MitoTempo delivery at the time of injury followed by tissue processing at 3 days after SCI. Control, SCI, and SCI-MitoTempo-treated mice were compared in all experimental conditions.

Corrigendum: Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis.

[This corrects the article DOI: 10.3389/fnsys.2018.

Involvement of TRPM4 in detrusor overactivity following spinal cord transection in mice.

Transient receptor potential cation channel subfamily M member 4 (TRPM4) has been shown to play a key role in detrusor contractility under physiological conditions. In this study, we investigated the potential role of TRPM4 in detrusor overactivity following spinal cord transection (SCT) in mice. TRPM4 expression and function were evaluated in bladder tissue with or without the mucosa from spinal intact (SI) and SCT female mice (T8-T9 vertebra; 1-28 days post SCT) using PCR, western blot, immunohistochemistry, and muscle strip contractility techniques.

The aging bladder insights from animal models.

Alterations in bladder function with aging are very common and are very likely to represent an increasing healthcare problem in the years to come with the general aging of the population. In this review the authors describe the prevalence of lower urinary tract symptoms (LUTS) and comment upon potential mechanisms which may be responsible for the increasing prevalence of lower LUTS with increasing age, based on laboratory studies. It is clear that there is a complex interplay between the various components of the neural innervation structure of the bladder in leading to changes with age, which are likely to underpin the LUTS which are seen in the aging bladder.

Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods.

Role of neurogenic inflammation in local communication in the visceral mucosa.

Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence supports the neural release of inflammatory factors, trophic factors, and neuropeptides in the initiation of inflammation. However, more recently, non-neuronal cells including epithelia, endothelial, mast cells, and paraneurons are likely important participants in nervous system functions.

Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged).

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients.

Urothelial proliferation and regeneration after spinal cord injury.

The basal, intermediate, and superficial cell layers of the urothelium undergo rapid and complete recovery following acute injury; however, the effects of chronic injury on urothelial regeneration have not been well defined. To address this discrepancy, we employed a mouse model to explore urothelial changes in response to spinal cord injury (SCI), a condition characterized by life-long bladder dysfunction. One day post SCI there was a focal loss of umbrella cells, which are large cells that populate the superficial cell layer and normally express uroplakins (UPKs) and KRT20, but not KRT5, KRT14, or TP63.

Pharmacodynamic evaluation of Lys, MeLeu, Nle-NKA prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats.

The purpose of this study was to determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK receptor) agonist, Lys, MeLeu, Nle-NKA (LMN-NKA). Cystometry and colorectal pressure measurements were performed in urethane-anesthetized, intact, and acutely spinalized female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity.

Increased urothelial paracellular transport promotes cystitis.

Changes in the urothelial barrier are observed in patients with cystitis, but whether this leads to inflammation or occurs in response to it is currently unknown. To determine whether urothelial barrier dysfunction is sufficient to promote cystitis, we employed in situ adenoviral transduction to selectively overexpress the pore-forming tight junction-associated protein claudin-2 (CLDN-2). As expected, the expression of CLDN-2 in the umbrella cells increased the permeability of the paracellular route toward ions, but not to large organic molecules.

Bladder smooth muscle strip contractility as a method to evaluate lower urinary tract pharmacology.

We describe an in vitro method to measure bladder smooth muscle contractility, and its use for investigating physiological and pharmacological properties of the smooth muscle as well as changes induced by pathology. This method provides critical information for understanding bladder function while overcoming major methodological difficulties encountered in in vivo experiments, such as surgical and pharmacological manipulations that affect stability and survival of the preparations, the use of human tissue, and/or the use of expensive chemicals. It also provides a way to investigate the properties of each bladder component (i.

Nitrergic relaxations and phenylephrine contractions are not compromised in isolated urethra in a rat model of diabetes.

In vivo experiments in a diabetic rat model revealed compromised nitrergic urethral relaxations and increased sensitivity to adrenergic agonists. This study evaluated contractile and relaxation properties of urethral smooth muscle after streptozotocin (STZ)-induced diabetes, in vitro, with the aim of determining whether in vivo deficiencies are related to smooth muscle dysfunction. Urethral tissue was collected from adult female Sprague-Dawley rats naive, STZ-treated, vehicle-treated and sucrose-fed at 9-12 week post treatment.

Excitatory effects of bombesin receptors in urinary tract of normal and diabetic rats in vivo.

Aims: Bombesin receptors (BB receptors) and bombesin related peptides are expressed in the lower urinary tract of rodents. Here we investigated whether in vivo activation of BB receptors can contract the urinary bladder and facilitate micturition in sham rats and in a diabetic rat model of voiding dysfunction.

Material And Methods: In vivo cystometry experiments were performed in adult female Sprague-Dawley rats under urethane anesthesia.

Functional bombesin receptors in urinary tract of rats and human but not of pigs and mice, an in vitro study.

Aims: Bombesin receptors (BB receptors) and/or bombesin related peptides are expressed in the lower urinary tract, though their function and distribution in different species is largely unknown. This study examines whether BB receptor agonists can contract bladder smooth muscle in rats, mice, pigs and humans.

Methods: Bladder strips were placed in tissue baths for in vitro contractility.

Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.

Effects of the 5-HT4 receptor agonist, cisapride, on neuronally evoked responses in human bladder, urethra, and ileum.

This study evaluated the effects of a 5-HT4 agonist, cisapride, on neuronally evoked smooth muscle responses in bladder, urethra and ileum and compared these effects with those of an acetylcholinesterase inhibitor, distigmine. Electrical field stimulation (EFS) was applied to human bladder and ileum smooth muscle strips from human organ transplant donors and to urethral strips from prostatectomy patients, to evoke neuronally mediated smooth muscle responses. EFS induced contractions in bladder and mixed responses, consisting of contractions and relaxations, in urethra and ileum.