Hiroki Chiba

Brain-bladder control network: The unsolved 21st century urological mystery

A review of functional brain imaging studies of bladder control in participants with normal control and pathological conditions. In the normal condition, bladder and urethral afferents received in the periaqueductal gray relay the information to the insula, the anterior cingulate cortex and the prefrontal cortex. During the storage phase, these superior regions control the pontine micturition center to inhibit voiding. In overactive bladder patients, brain responses are different. Cortical responses become exaggerated, especially in the anterior cingulate cortex and the supplementary motor area. That is what presumably evokes the “urgency”. The supplementary motor area is activated during contraction of the pelvic floor muscles, and provides protection against incontinence. We believe that functional brain imaging studies are promising not only for the understanding of bladder dysfunction, but also as an aid to the development of therapeutic options for chronic disorders.

Postoperative detrusor contractility temporarily decreases in patients undergoing pelvic organ prolapse surgery

To assess the postoperative lower urinary tract function in patients undergoing pelvic organ prolapse surgery.

Differences in neurotransmitter systems of ventrolateral periaqueductal gray between the micturition reflex and nociceptive regulation: An in vivo microdialysis study

To elucidate the possible involvement of glutamate and serotonin (5‐hydroxytryptamine) neurons in the ventrolateral midbrain periaqueductal gray during noxious stimulation.

Radical prostatectomy restores detrusor contraction pattern according to pressure flow parameters

Pressure flow studies are regarded as the gold standard for evaluating both bladder outlet obstruction and detrusor contractility, but none of the current methods for evaluating bladder contraction patterns are well validated. Impaired bladder contraction results in a lower peak Watts factor and poorly sustained detrusor contractions. From this viewpoint, the maximum Watts factor and its pattern should be considered separately. To examine detrusor contraction pattern in patients after radical prostatectomy by using multiple parameters.

The role of serotonergic mechanism in the rat prefrontal cortex for controlling the micturition reflex: an in vivo microdialysis study

To investigate the role of the PFC in the micturition reflex using an in vivo microdialysis study in rats.

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research

The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value.

Long-term impact of unilateral hypo/dysplastic kidney in infants with primary vesicoureteral reflux

INTRODUCTION Renal abnormality is not a rare finding in infants with primary VUR. The pathophysiology of the renal abnormality is considered to be congenital or acquired. Congenital hypo/dysplastic kidney is a common finding in infants with primary VUR, especially in boys. However, the long-term impact of unilateral hypo/dysplastic kidney has not been elucidated. The aim of the current study is to clarify the long-term impact of unilateral hypo/dysplastic kidney with primary vesicoureteral reflux diagnosed in infancy. MATERIAL AND METHODS The medical records of patients with primary VUR detected in infancy with unilateral hypo/dysplastic kidney on initial nuclear renal scan (<40% relative renal function) and no scar on the contralateral kidney were reviewed retrospectively. Among them, 29 patients who were followed for more than 5 years were included in this study. Their clinical outcomes including chronic kidney disease (CKD) stage using estimated glomerular filtration rate (GFR) and the incidences of hypertension and proteinuria were analyzed. RESULTS Mean age at final visit was 12.4 years (range 5.9-22.2). Estimated GFR was evaluated in 26 patients at a mean age of 12.0 years (5.9-22.2). CKD stage was 1 in all. According to the guidelines of the Japanese Society of Hypertension, while none exceeded the standard level of systolic blood pressure (BP), two patients slightly exceeded the standard level of diastolic BP. In addition, no significant proteinuria was detected in all patients, although microalbuminemia was detected in 7.7% of patients. DISCUSSION The prognosis of reflux nephropathy depends on the remnant renal tissue mass, that is, the number of normal nephrons. The normal congenital solitary kidney is reported to be hyperplastic with normal-sized glomeruli rather than hypertrophic ones with larger nephrons, and to have better long-term outcome regarding renal function. Accordingly, we speculated that patients with unilateral hypo/dysplastic kidney would have a similar number of nephrons to those without hypo/dysplastic kidney who have no or minimal scar as far as the contralateral kidney is well preserved. Long-term outcome of the current retrospective study was consistent with our speculation in terms of estimated GFR, proteinuria, or hypertension. CONCLUSIONS The present study demonstrated that significant clinical findings related to unilateral hypo/dysplastic kidney detected in infancy were rarely observed in the long term. Accordingly, unilateral hypo/dysplastic kidney seems to be a benign condition. To confirm this finding, further follow-up of these patients is necessary.

MP19-11 EFFECTS OF CHRONIC BLOCKADE OF ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONATE (AMPA) GLUTAMATERGIC RECEPTORS ON NEUROPLASTICITY OF THE MICTURITION REFLEX PATHWAY AFTER PARTIAL URETHRAL OBSTRUCTION IN THE RAT

INTRODUCTION AND OBJECTIVES: In the rat partial urethral obstruction produces bladder hypertrophy and hyperactive voiding. We previously reported that Alpha-amino-3-hydroxy-5-methyl-4isoxazolepropionate (AMPA) glutamatergic receptors are thought to participate in the control of micturition in bladder outlet obstruction (BOO) rats (AUA 2007). To determine the role of AMPA receptors in the development of functional bladder changes after partial urethral obstruction we investigated the effects of chronic administration of CFM-2, a specific AMPA receptor antagonist, on the micturition reflex in conscious BOO rats. METHODS: In female Wistar rats osmotic pump ware implanted just prior to the creation of partial urethral obstruction until 4 weeks after obstruction (0.07mg/kg, or 0.70mg/kg per day). Seven days after the pump was stopped conscious filling cystometry was performed and compared with that in obstructed rats treated with vehicle. Conscious filling cystometry was also compared in sham operated rats treated CFM-2 and vehicle, respectively. RESULTS: Partial urethral obstruction caused a significant increase in bladder weight. However, chronic CFM-2 treatment did not affect bladder weight in obstructed or sham operated rats. In the obstructed/ CFM-2 vs the obstructed/vehicle group chronic treatment with CFM-2 significantly increased bladder capacity and voided volume without changes in voiding efficiency or micturition pressure (Table). However, neither the frequency nor amplitude of premicturition contractions (PMCs: associated with increased activation of sensory nerve endings, resulting in urgency) was not significantly changed chronic treatment with CFM-2. In sham operated rats chronic CFM-2 treatment did not change any parameters (Table). CONCLUSIONS: The results in the current study suggest that BOO causes AMPA receptor mediated alterations in bladder afferent pathways in the rat. However, generations of PMCs have linked to other mechanisms.