Background and purpose. Recent studies have shown that the children with severe nocturnal enuresis, or bedwetting, often have underlying bladder dysfunction as well as various types of brainstem disorders, including arousal inability, a deficient response to startle sounds, or prepulse inhibition. Since the pontine micturition centre is anatomically very close, even overlapping with the nuclei responsible for sleep arousal, one may speculate that there may be close inter-relationships between abnormal bladder function, brainstem dysfunction and sleep-arousal disturbance. We hypothesize that the brainstem function would be changed in response to alteration of bladder function. Using conventional-fill cystometric study, functional magnetic resonance imaging (fMRI) scanning and immunohistochemistry approaches, we propose to characterize the functional changes in the brainstem in response to altered bladder function (i.e. surgically reduced bladder capacity). / Conclusions. Our results showed that bladder dysfunction elicited by surgical reduction in bladder capacity can induce functional changes in the central nervous system. In response to surgical reduction in bladder capacity, deactivation in the vlPAG was detected suggesting that the vlPAG plays a role in the biofeedback of bladder dysfunction. / Data are expressed as the mean +/-1SD unless otherwise specified. Appropriate statistical tests were used for parametric and non-parametric testing between the groups by using the SPSS computer program. In all comparisons a statistical significance level of 95% (p<0.05) was chosen. / Immunohistochemistry study showed a significant decrease in the reaction of dopaminergic neuron in the correspondent regions, suggesting a dopaminergic dependent change in the vlPAG in response to the bladder dysfunction. / In addition, we will explore the use of electroacupuncture (EA), a traditional Chinese therapy that has been broadly used for treatment of bladder functional disorders, to modulate functional changes in the central nervous system. We hypothesize that functional change in various nuclei in the central nervous system that are responsible for micturition control can also be affected by acupuncture treatment. A further aim of this study was to identify brain areas involved in EA to acupoint Chiliao (BL 32), a special acupoint broadly used for the treatment of bladder disorders. / Materials and methods. The study was divided into four parts. Seventy-five male New Zealand white rabbits (14-16 weeks, mean body weight: 3.0-3.5 kg) were used. / Moreover, in this study, we also found a notable activation in the vlPAG and dlPONS in response to the acupuncture stimulations to acupoint Chiliao (BL 32). The changes were identical to that induced by the bladder distension, suggesting a neuromodulation in central nervous system in response to acupuncture therapy. / Results. Study I: Bladder dysfunction elicited by surgical reduction in bladder capacity. Compared to sham animals, the maximum cystometric capacity in animals with RBC operation was markedly decreased at week 4 (35.3+/-8.2 ml vs. 71.6+/-12.9 ml, p<0.05), and week 8 (46.2+/-12.1ml vs. 82.7+/-20.1 ml, p<0.05) groups respectively; however, the maximum voiding detrusor pressure was significantly increased at week 4 (24.4+/-7.0 vs.16.5+/-7.2 cm water, p<0.05) and week 8 (27.7+/-8.p vs. 16.8+/-7.5 cm water, p<0.05) groups respectively, and their corresponding vesical pressure was also enhanced. Other parameters including maximum flow rate, and bladder emptying efficiency did not change significantly in between the sham and RBC subgroups. / Study I: Establishment of the dysfunctional bladder animal model with small bladder capacity. Forty rabbits underwent either sham operation (n=20) or operation for reduced bladder capacity (RBC) (n=20). The sham-operated and the RBC animals were further divided into two groups, i.e. four, and eight weeks after operation (n=10 in each sham and RBC subgroup). A conventional-fill cystometric study was performed on these animals whilst awake in order to evaluate the functional changes (if any) in response to surgical bladder capacity reduction, compared to sham subgroup. / Study II: Detection of functional changes in the brainstem in response to bladder dysfunction. FMRI scanning was performed at the brainstem region in sham-operated and RBC rabbits (12 in each group) at four weeks postoperatively. Bladder stimulation was provided by warm saline (37°C) infusion through a urethral catheter until bladder distended to 70% of the maximum capacity. Area(s) of brainstem activation were assessed by comparing the fMRI scans performed before and after warm saline infusion. / Study II: Functional changes in brainstem in response to bladder dysfunction. FMRI scanning results demonstrated that for the sham animals, there were two activated regions in the brainstem in response to bladder distention, one in the ventrolateral region of periaqueductal gray (vlPAG, 83.3%, 10/12), and the other in the dorsolateral region of pons (dlPONS, 91.7%, 11/12). In animals with RBC operation, only 25% (3/12) showed vlPAG activation compared to 83.3% (10/12) in sham group (p<0.05); however, 83.3% (10/12) of animals showed similar dlPONS activation compared to 91.7% in sham group (p>0.05). / Study III: Catecholaminergic neurotransmitters changes in the brainstem affected areas in response to bladder dysfunction. Brainstem immunohistochemistry results showed that a large number of dopaminergic neuron scattered throughout the whole vlPAG, rarely appeared in dlPAG (dorsolateral region of periaqueductal gray) (lambda +6.0 to +3.0 mm); and an abundant noradrenergic neurons were also accumulated in a restricted region of dlPONS (lambda +3.0 to 0 mm). Compared with the sham group, the density of TH-positive neurons in the vlPAG was significantly decreased in RBC group (38.38+/-4.71 vs.51.57+/-8.38/field, p<0.05); for the another region of dlPONS, although the density of TH-positive neurons decreased slightly in RBC group compared to sham group, the results showed no statistical difference between groups (106.89 +/- 21.61 vs.120.61 +/- 17.03/field, p>0.05). / Study III: Investigation of the catecholaminergic neurotransmitters changes in brainstem affected areas in response to bladder dysfunction. After fMRI examination, all animals were euthanized, and their brainstems were collected for immunohistochemistry study with tyrosine hydroxylase, dopamine-beta-hydroxylase assays to investigate the changes of catecholaminergic neurotransmitters including dopaminergic, noradrenergic and adrenergic in response to bladder dysfunction elicited by surgical reduction in bladder capacity. / Study IV: Electroacupuncture modulation via acupoint Chiliao (BL 32) on bladder and the brainstem activated sites. FMRI study showed that the two brainstem micturition centers of the vlPAG (72.7%, 8/11) and dlPONS (82.8%, 9/11) can be activated by EA on BL 32, and there were no significant difference compared with stimulation of bladder distention (72.7% vs. 83.3% in vlPAG and 82.8% vs. 91.7% in dlPONS respectively, p>0.05). Urodynamic results showed that, bladder contraction obviously evoked in response to EA on BL 32 (ON-EA state) compared to before EA state (OFF-EA state), displaying a significantly increased detrusor pressure (14.04+/-3.17 vs. 8.19+/-0.69 cm water, p<0.05) and vesical pressure (13.48+/-1.61vs. 7.90+/-0.81 cm water, p<0.05). In addition, dissection of BL 32 showed that the stem of S1 and S2 pass through the region 0.5 cm around the acupuncuture needle. / Study IV: Investigation of electroacupuncture modulation via acupoint Chiliao (BL 32) on bladder and the brainstem activated sites. FMRI scanning and urodynamic evaluation were performed respectively during ON/OFF EA on acupoint Chiliao (BL 32) on sham-operated animals (n=12) at four weeks post-operation. At last, dissection of acupoint BL 32 was performed on seven sham animals. / We also found that surgically induced bladder dysfunction, mainly displaying as reduced bladder capacity and maximum voiding detrusor pressure enhanced, was elicited at four to eight weeks after the surgical reduction in bladder capacity in rabbit. / Xiang Bo. / "August 2006." / Adviser: Chung Kwong Yeung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1551. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 161-196). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343856 |
| Date | January 2006 |
| Contributors | Xiang, Bo., Chinese University of Hong Kong Graduate School. Division of Surgery. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xxvi, 196 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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