Biomedical subjects

Satoshi Seki

Publications and source records attributed to Satoshi Seki.

18 recordsLinked to original sources

PubMed2006

Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats.

Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 microg/microl) was infused continuously into the intrathecal space at the L6-S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 microl/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6-S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.

Animals↗

PubMed2006

Dopaminergic mechanisms controlling urethral function in rats.

AIMS: To investigate the role of dopamine receptor subtypes in the control of urethral activity. METHODS: Simultaneous recordings of intravesical and urethral perfusion pressure (UPP) were performed in rats under urethane anesthesia. Changes in coordinated activity of the bladder and urethral sphincter were examined following intravenous (i.v.), intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration of dopamine D1- and D2-like receptor agonists (SKF38393 and quinpirole, respectively) and antagonists (SCH23390 and remoxipride, respectively). RESULTS: Quinpirole (0.03, 0.1, and 0.3 mg/kg i.v.) dose-dependently decreased baseline urethral pressure to 45.33 +/- 5.8, 33.7 +/- 3.3 (P < 0.05, n = 6), and 27.7 +/- 3.3 cm H(2)O (P < 0.05, n = 5) from the control value (46.0 +/- 4.0 cm H(2)O), respectively. i.c.v. injection of quinpirole (1 microg) decreased baseline urethral pressure to 33.6 +/- 5.0 cm H(2)O (P < 0.05, n = 4) from the control value (51.4 +/- 4.9 cm H(2)O) in contrast to the insignificant effects of i.t. administration of the drug (3 microg). The decrement of baseline pressure induced by quinpirole (0.1 mg/kg i.v.) was suppressed by alpha-bungarotoxin (BGT), a neuromuscular blocking agent. SCH23390 (1 and 3 mg/kg, i.v.) dose-dependently decreased the frequency of high frequency oscillation (HFO) of the urethral sphincter. SKF38393 or remoxipride did not have significant effects on any parameters of bladder and urethral activity. CONCLUSIONS: These results indicate that activation of D2-like dopamine receptors at a supraspinal site can suppress activity of the striated muscle urethral sphincter. Thus, decreased urethral resistance induced by D2 dopamine receptor activation might aggravate urge incontinence symptoms often seen in patients with Parkinson's disease (PD).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2006

Rotational and translational reproducibility of newly developed Leksell frame-based relocatable fixation system.

PURPOSE: The aim of this study was to evaluate three-dimensional movement of the cranium in a relocatable frame using positions of anatomical landmarks obtained from repeated quality-assurance (QA) computed tomography (CT) studies. MATERIALS AND METHODS: We analyzed 17 series of QA-CT data representing five patients who underwent stereotactic radiotherapy for treatment of acoustic neurinoma. Helical-CT scans with 1-mm collimation were obtained at the time of treatment planning and during the course of treatment. The right and left short processes of the incus and the top of the crista galli were used as the three anatomical reference points. RESULTS: Fluctuations in distance among the reference points were all <1 mm. The translational displacements for these points were <2 mm, with standard deviations (SD) of <2 mm. A plane that included all three reference points was defined as the reference plane. To investigate the direction of cranial rotation for each QA-CT scan, unit normal vectors of the reference plane were obtained. Three-dimensional analyses indicated that cranial rotation was greatest along the X-axis, followed by the Y-axis, with the least rotation along the Z-axis. CONCLUSION: The result suggested that movement of the craniocaudal axis in the sagittal plane was a major factor behind displacement of the cranium.

Adult↗

PubMed2005

Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation.

Substance P (SP) binding to neurokinin 1 receptors (NK1R) in the spinal cord reportedly plays an important role in the micturition reflex as well as in nociceptive responses. We therefore investigated the effect of ablation of NK1R-expressing neurons in the spinal cord using saporin, a ribosome-inactivating protein, conjugated with [Sar9, Met (O2)11]SP, a specific ligand of NK1R (SSP-saporin), on the micturition reflex in rats. In female Sprague-Dawley rats, SSP-saporin (1.0 or 1.5 microM) or saporin (1.5 microM) only was injected through an intrathecal catheter implanted at the L6-S1 level of the spinal cord. Three weeks after intrathecal administration of SSP-saporin, NK1R immunoreactivity in lamina I of the spinal cord was significantly reduced, but cystometric parameters in awake rats were not altered. Instillation of capsaicin (15 microM) into the bladder of normal rats induced bladder overactivity. This response to capsaicin was significantly suppressed in SSP-saporin-treated animals. SSP-saporin treatment also decreased c-fos expression in the dorsal horn of the spinal cord induced by instillation of capsaicin into the bladder. These data indicate that NK1R-expressing neurons in the superficial layer of the dorsal horn play an important role in transmission of nociceptive afferent information from the bladder to induce bladder overactivity and spinal c-fos expression elicited by bladder irritation. Toxin-induced damage of NK1R-expressing neurons in the lumbosacral spinal cord may provide an effective modality for treating overactivity and/or nociceptive responses in the bladder without affecting normal micturition.

Animals↗

PubMed2005

[Congenital anterior cervical fistula originating from the Wharton duct].

A 14-year-old boy presented with a spontaneous anterior cervical fistula, which exuded a saliva-like fluid during eating. Cervical examination revealed a hole 7 mm posterior to the hyoid bone, 5mm left of the median. Magnetic resonance imaging showed a low-intensity spindly mass with high-intensity margins. The mass was connected to the left submandibular gland. Contrast radiography of the fistula using Gastrografin demonstrated an ascending fistula that extended to the submandibular area. Intraoperatively, the fistula was shown to have ascended superficial to the level of the anterior cervical muscles, and it formed a cyst anterior to the hyoid bone. It then continued to the left submandibular gland. The fistula and submandibular gland were removed together. Wharton's duct was not found, and the orifice of the duct was unclear. Pathological examination of the fistula showed the lining epithelium at the side of the submandibular gland to be composed of columnar epithelial cells with stratified squamous cells at the epidermal side. Several acinar systems were found along the orifice of the fistula. There have been no previous reports of the Wharton duct running from the submandibular gland to the anterior cervical skin.

Adolescent↗

PubMed2004

Lymphoscintigraphy for the visualization of sentinel lymph nodes and body contour.

BACKGROUND: It is important to create clear lymphoscintigraphic images when assessing the sentinel lymph nodes. This clarity needs to reach a level where the sentinel lymph nodes (SLNs) and the body contour are clearly visible. We have developed a simple image processing method using the division of primary and scattered photon counts. METHODS: Twenty patients with breast cancer were enrolled in this study. Manual injection of 150 MBq of Tc-99m tin colloid with small particle size into the peritumoral and subdermal regions was performed. Lymphoscintigraphy using a conventional gamma camera was performed three hours after the injection. Dual energy windows were set from 130 to 150 keV for the primary photons and 70 to 110 keV for the scattered photons. An anterior view of the chest and a lateral view from the affected side were obtained. Primary photon image counts were divided by the scattered photon image counts for each pixel after the addition of some constant counts to each pixel of the acquired image to improve the contrast of the scintigrams. We evaluated the ability to accurately visualize the body contour and the SLNs on the processed image. RESULTS: Image processing time was 20 to 40 seconds for each patient. In every case, the processed image clearly identified the body contour. The processed images allowed the identification of the same number of SLNs as the original images. CONCLUSIONS: This proposed method for image processing is a simple and useful means to clearly visualize both SLNs and body contours.

Adult↗

PubMed2004

Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats.

PURPOSE: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (NGF-Abs) and desensitization of C-fiber afferent pathways by capsaicin treatment on detrusor-sphincter dyssynergia (DSD) after spinal cord injury (SCI). MATERIALS AND METHODS: In adult female rats SCI was induced by complete transection of the spinal cord at Th8 to 9. Ten days after spinalization vehicle or NGF-Ab (10 microg daily) was continuously administered at the level of the L6-S1 spinal cord through an implanted intrathecal catheter connected to an osmotic pump for 2 weeks. Another group of spinalized rats was treated with capsaicin (125 mg/kg subcutaneously) 3 weeks after spinalization and 5 days before experiments. Simultaneous recordings of intravesical pressure and urethral perfusion pressure were then performed. NGF levels in the L6 spinal cord were measured in vehicle or NGF-Ab treated spinalized rats using enzyme-linked immunosorbent assay. RESULTS: DSD was observed in all vehicle treated spinalized rats. The average urethral pressure increase at the peak bladder contraction was significantly lower by 84% and 78% in NGF-Ab and capsaicin treated spinalized rats, respectively, than in vehicle treated rats. After NGF-Ab treatment NGF levels were significantly decreased by 38% in the L6 spinal cord compared with vehicle treated spinalized rats, in which NGF levels in the L6 spinal cord were 7 times higher than in spinal intact rats. CONCLUSIONS: Increased levels of NGF in the spinal cord could contribute to the emergence of DSD that is at least in part mediated by C-fiber bladder afferents after SCI. Thus suppression of NGF levels in afferent pathways could be useful for treating DSD following SCI.

Afferent Pathways↗

PubMed2004

Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats.

PURPOSE: We investigated the effects of endothelin (ET) receptor activation in the bladder and the spinal cord on the micturition reflex in urethane anesthetized rats. MATERIALS AND METHODS: The effects of ET receptor activation on bladder activity were examined during continuous infusion cystometrograms. ET-1 was administered intrathecally or intravesically in normal rats or rats pretreated with capsaicin. The effects of intravenous injection of the selective ETA receptor antagonist ABT-627, or selective ETB receptor antagonist A-192621 (Abbott Laboratories, Abbott Park, Illinois) intrathecal injection of the opioid receptor antagonist naloxone hydrochloride on changes in bladder activity induced by intravesical or intrathecal ET-1 administration were investigated. RESULTS: Intravesical injection of ET-1 (0.1 to 10 microM) induced detrusor overactivity, as evidenced by a decrease in intercontraction intervals, in a dose dependent manner. ET-1 induced detrusor overactivity was suppressed by intravenous application of ABT-627 (0.1 mg/kg) as well as capsaicin pretreatment but not by A-192621. In contrast, intrathecal injection of ET-1 (0.5 to 50 fmol) increased intercontraction intervals dose dependently and ET-1 at a higher dose (50 fmol) induced urinary retention. These inhibitory effects were antagonized by ABT-627 (10 mg/kg) and also by intrathecal application of naloxone but not by A-192621. CONCLUSIONS: These results indicate that the activation of ETA receptors in capsaicin sensitive C-fiber afferents in the bladder can induce detrusor overactivity, while ETA receptor activation in the spinal cord can inhibit the micturition reflex via activation of a spinal opioid mechanism. Thus, targeting peripheral ETA receptors could be an effective treatment for bladder overactivity and/or painful conditions.

Afferent Pathways↗

PubMed2004

Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation.

In order to clarify the functional role of the isolectin B4 (IB4)-binding afferent pathway in the micturition reflex, we investigated the effects on bladder activity of intrathecal application of the IB4-saporin conjugate, a targeting cytotoxin that destroys neurons binding IB4. In rats, IB4-saporin (2.5 micro m) or vehicle was administered through an intrathecal catheter implanted at the level of the L6-S1 spinal cord. Three weeks after IB4-saporin administration, cystometry in conscious animals revealed a reduction in bladder overactive responses induced by intravesical capsaicin or ATP infusion without affecting normal voiding function. In histochemical studies, double staining for IB4 and saporin was detected in L6 dorsal root ganglia (DRG) neurons 2 days after the treatment. Three weeks after the treatment, the area in lamina II of the L6 spinal cord stained with IB4 was significantly reduced compared with the area stained in control rats. The staining in the L1 spinal cord was not affected. The percentage of neurons in the L6 DRG intensely labeled with IB4 was also reduced in IB4-saporin-treated rats. These results indicate that intrathecal treatment with the IB4-saporin conjugate at the level of L6-S1 spinal cord, which reduces IB4 afferent nerve terminal staining in lamina II of the L6 spinal cord as well as the number of IB4-binding neurons in L6 DRG, suppressed bladder overactivity induced by bladder irritation without affecting normal micturition. Thus targeting IB4-binding, non-peptidergic afferent pathways sensitive to capsaicin and adenosine 5'-triphosphate may be an effective treatment for overactivity and/or pain responses in the bladder.

Adenosine Triphosphate↗

PubMed2004

[A difficult case of advanced testicular choriocarcinoma effectively treated by chemotherapy and resection of lung metastasis].

A 25-year-old man who suffered from cough, sputum, and swelling of left scrotal contents was admitted to our hospital. We found testicular choriocarcinoma with multiple lung, liver, and brain metastases. The patient received 5 courses of VIP therapy (cisplatin, etoposide, ifosfamide) and 1 course of high-dose chemotherapy (carboplatin, etoposide, cyclophospamide) with peripheral blood stem cell transplantation. One year later, the patient underwent surgery for resection of lung metastasis after 1 course of chemotherapy (cisplatin, etoposide). Pathological diagnosis showed a remnant of choriocarcinoma. Three years and three months after surgery, no recurrence of the choriocarcinoma has been found.

Adult↗

PubMed2003

Histological and electrical properties of rat dorsal root ganglion neurons innervating the lower urinary tract.

We investigated whether primary afferent neurons innervating different regions of the lower urinary tract have different histochemical and electrophysiological properties. Neurons in rat L6-S1 DRG were identified by axonal transport of a fluorescent dye. Neurofilament-negative C-fiber cells comprise approximately 70% of bladder and proximal urethral afferent neurons that send axons through the pelvic nerves, but comprise a smaller proportion (51%) of distal urethral neurons that send axons through the pudendal nerves. Isolectin-B4 (IB4) binding was detected in a higher percentage (49%) of C-fiber neurons innervating the distal urethra than in those innervating the bladder or proximal urethra (18-22%). Neurofilament-positive A-fiber neurons innervating the distal urethra had a larger average somal size than neurons innervating the bladder or proximal urethra. In patch-clamp recordings, the majority (70%) of bladder and proximal urethral neurons were sensitive to capsaicin and exhibited TTX-resistant, high-threshold action potentials, whereas a smaller proportion (53%) of distal urethral neurons exhibited TTX-resistant spikes. T-type Ca2+ currents were observed in 47% of distal urethral neurons with TTX-sensitive spikes, but not in TTX-sensitive bladder or proximal urethral neurons. In summary, afferent neurons innervating bladder or proximal urethra differ from those innervating distal urethra. The latter, which more closely resemble cutaneous afferent neurons, consist of a smaller number of C-fiber neurons containing a higher percentage of IB4-positive cells and a more diverse population of A-fiber neurons, some of which exhibit T-type Ca2+ channels. These differences may be related to different functions of respective target organs in the lower urinary tract.

Amidines↗

PubMed2003

Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity.

OBJECTIVES: An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl). METHODS: Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. RESULTS: Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects. CONCLUSIONS: Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents. Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity.

Administration, Intravesical↗

PubMed2003

Changes in spontaneous firing rate and neural synchrony in cat primary auditory cortex after localized tone-induced hearing loss.

Increase in spontaneous neural activity after noise-induced hearing loss has frequently been associated with the phenomenon of tinnitus. Eighteen juvenile and adult cats were exposed for 2 h to a 6 kHz tone with an intensity of 115 dB SPL at the cat's head. Seven non-exposed littermates and seven other normal hearing cats were used as age-matched controls. The trauma cats showed localized hearing losses, as assessed by ABR, ranging from less than 20 to 60 dB. The frequency representation in primary auditory cortex was mapped using an eight-electrode array. Single-unit spontaneous activity was recorded for 15 min. Peak cross-correlation coefficients (R) for unit cluster activity recorded on separate electrodes were calculated. We found elevated spontaneous firing rates in regions with reorganization of the tonotopic map compared to the neurons in the non-reorganized cortical regions in the same animals. A second finding was that in these regions the peak cross-correlation coefficients were also increased relative to the non-reorganized parts. A third finding was that exposed animals showed higher spontaneous activity compared to controls regardless of the presence of cortical reorganization. This may be a correlate of tinnitus in the presence of only minor hearing losses.

Acoustic Stimulation↗

PubMed2003

Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway.

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2002

Immunoneutralization of nerve growth factor in lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats.

PURPOSE: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (Ab) on bladder hyperreflexia in chronic spinalized rats. MATERIALS AND METHODS: In adult female rats an intrathecal catheter was implanted at the level of the L6 to S1 spinal cord, followed by complete transection of the Th8 to 9 spinal cord. At 10 days after spinalization the intrathecal catheter was connected to an osmotic pump for continuous delivery of vehicle or NGF Ab (10 microg daily) for 2 weeks. Awake cystometry was then performed. NGF levels in the L5 to S1 dorsal root ganglia, L6 spinal cord and bladder were also measured using enzyme-linked immunosorbent assay. RESULTS: The number of uninhibited bladder contractions per voiding cycle, maximal pressure of uninhibited bladder contraction and maximal voiding pressure were significantly decreased in NGF Ab treated versus vehicle treated spinalized rats. Intercontraction interval, baseline intravesical pressure, pressure threshold for voiding and voiding efficiency were not significantly changed by NGF Ab treatment. NGF levels in the bladder, L6 spinal cord and L5 to S1 dorsal root ganglia of vehicle treated spinalized rats was 1.6 to 4.8 times higher than in spinal cord intact rats. After intrathecal NGF Ab treatment NGF levels were significantly lower in the L6 to S1 dorsal root ganglia (30% to 35%) and L6 spinal cord (53%) but not in the bladder or L5 dorsal root ganglia compared with levels in vehicle treated spinalized rats. CONCLUSIONS: Increased levels of NGF in the bladder, spinal cord and dorsal root ganglia were associated with bladder hyperreflexia after spinal cord injury. Immuno-neutralization of NGF in the spinal cord suppressed NGF levels in the L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, and also suppressed bladder hyperreflexia. Thus, suppression of NGF levels in afferent pathways could be useful for treating bladder hyperreflexia associated with spinal cord injury.

Afferent Pathways↗

PubMed2002

Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root Ganglia.

PURPOSE It has been proposed that a deficiency in the axonal transport of nerve growth factor (NGF) may have an important role in inducing diabetic neuropathy, which contributes to diabetic cystopathy. Therefore, in streptozotocin (Sigma Chemical Co., St. Louis, Missouri) induced diabetic rats we investigated the relationship of bladder function with NGF levels in the bladder and lumbosacral dorsal root ganglia, which contain afferent neurons innervating the bladder. MATERIALS AND METHODS At 6 and 12 weeks after the induction of diabetes with streptozotocin (65 mg./kg. intraperitoneally) the effects of diabetes on Adelta afferent fiber dependent, conscious voiding were evaluated by metabolic cage measurements and awake cystometry. The effects of diabetes on C-fiber mediated bladder nociceptive responses were also investigated by cystometry with intravesical instillation of 0.25% acetic acid in the rats under urethane anesthesia. NGF levels in the bladder and L6 to S1 dorsal root ganglia were measured by enzyme-linked immunosorbent assay 3, 6, 9 and 12 weeks after streptozotocin injection. RESULTS In diabetic rats NGF levels in the bladder and L6 to S1 dorsal root ganglia were significantly decreased 12 weeks after streptozotocin injection (p <0.01). In cystometry and metabolic cage studies bladder capacity and post-void residual volume were significantly increased 12 weeks after streptozotocin injection (p <0.01). Bladder nociceptive responses revealed by a reduction in inter-contraction intervals after acetic acid infusion were significantly decreased in a time dependent manner 12 weeks after streptozotocin injection.CONCLUSIONS Rats with streptozotocin induced diabetes mellitus showed a significant time dependent decrease in NGF levels in the bladder and L6 to S1 dorsal root ganglia that was associated with voiding dysfunction attributable to defects in Adelta and C-fiber bladder afferents. Therefore, reduced production of NGF in the bladder and/or impaired transport of NGF to L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, may be an important mechanism inducing diabetic cystopathy.

Animals↗

PubMed2002

Targeting afferent hyperexcitability for therapy of the painful bladder syndrome.

The involvement of C-fiber afferent pathways in urinary frequency and pain associated with painful bladder syndrome raises the possibility of multiple targets for the treatment of this disease. Using an in vivo measurement of bladder activity as well as whole-cell patch clamp recording techniques to examine the properties of bladder afferent neurons in animal models of chronic cystitis, we have documented that tetrodotoxin-resistant sodium channels encoded by the Na(v) 1.8 (PN3/SNS) gene and nitric oxide acting via a cyclic guanosine monophosphate (cGMP)-dependent mechanism are important in modulating bladder pain responses. Thus, suppression of C-fiber afferent nerve activity by blocking specific sodium channels, elevating nitric oxide levels, or activating cGMP-dependent pathways might represent novel strategies for the treatment of symptoms in patients with painful bladder syndrome. Another treatment strategy is suppression of release or activity of proinflammatory agents that can cause normally unexcitable C-fiber afferents to become hyperactive or hyperexcitable. This approach to management of bladder pain was tested in patients with painful bladder syndrome by examining the effectiveness of the antiallergic agent suplatast tosilate (IPD-1151T), which suppresses urinary frequency in a rat model of cystitis. IPD-1151T is an immunoregulator that suppresses cytokine production in T-helper 2 cells and inhibits immunoglobulin E antibody formation and antigen-induced histamine release from mast cells. Preliminary data from an open-label clinical trial showed that 16 of 23 (70%) patients responded to treatment with IPD-1151T (300 mg/day orally for 12 months). The finding that expression of platelet-derived endothelial cell growth factor, which can activate mast cells, was lower in the bladder of responders than nonresponders indicates that bladder levels of platelet-derived endothelial cell growth factor may be a useful marker for this disease.

Afferent Pathways↗

PubMed2002

Changes in cat primary auditory cortex after minor-to-moderate pure-tone induced hearing loss.

In this paper we present findings in the primary auditory cortex of cats exposed for 2 h to a 115 dB SPL, 6 kHz tone at 36 days, 56 days or 118 days after birth. We evaluate the effects of age at exposure, amount of hearing loss, and time after induction of trauma on the functional reorganization of the cortical tonotopic map. We found a fairly sharp demarcation in the amount of hearing loss (20-25 dB) that caused cortical reorganization. For localized hearing losses, unmasking of excitatory contributions of neighboring frequency regions was found. For cats showing reorganization of the tonotopic map, the frequency-tuning curve bandwidth at 20 dB above threshold at CF (BW(20dB)) increased with increasing threshold at CF. Threshold at CF, and BW(20dB) increased with time after exposure. Minimum spike latency was initially increased, but subsequently decreased with time after exposure at a rate that was two times faster in cats with reorganized cortex than in cats with normal tonotopic maps, to reach the same asymptotic value. Thresholds at CF were correlated with the peripheral hearing loss at near CF frequencies as estimated from ABR measurements. The correlation between BW(20dB) and CF threshold suggests that part of the reorganization could be due to 'residual' sensitivity of the high frequency neurons to not-affected lower or higher frequencies. However, for CFs above 6 kHz, the BW(20dB) for cats with reorganization of the tonotopic map was significantly lower (on average 0.3 octave, P<0.05) than for cats with normal tonotopic maps. This is not what one would expect in cases of pseudo-plasticity characterized by concurrent shifts in BW(20dB) and CF as a result of residual sensitivity to lower frequencies.

Action Potentials↗