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Effects of liposome-based local suppression of nerve growth factor in the bladder on autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury.

ABSTRACT: To examine (1) whether spinal cord injury (SCI) time-dependently increases the severity of autonomic dysreflexia (AD) and expression levels of bladder nerve growth factor (NGF) protein, and (2) whether local suppression of NGF in the bladder improves SCI-induced AD in rats.SCI was produced by the transection of the T2/3 spinal cord in female Sprague-Dawley rats. At 4 or 8weeks after SCI, differences in the mean arterial blood pressure (ΔMAP) and heart rate (ΔMHR) during graded increases in intravesical pressure to 20, 40 and 60cm H2O from those before bladder distention and NGF protein levels in the bladder wall were evaluated in spinal intact and SCI rats under urethane anesthesia. Seven weeks after SCI liposome-NGF antisense conjugates were administered intravesically to the animals. At 1week after intravesical treatment (8weeks after SCI), ΔMAP and ΔMHR during bladder distention and bladder NGF protein expression were evaluated.The ΔMAP and ΔMHR were increased in a graded manner in response to bladder distention at intravesical pressures of 20, 40 and 60cm H2O in SCI rats. These AD-like cardiovascular responses and NGF protein expression in the bladder mucosal and muscle layers were increased after SCI in a time-dependent manner. The liposome-NGF antisense treatment significantly reduced the NGF protein overexpression in the mucosal layer of SCI rat bladder and reduced ΔMAP and ΔMHR elicited by bladder distention.These results indicate that the duration of the post-SCI recovery period affects the severity of AD induced by bladder distention as well as the level of bladder NGF protein, and that local suppression of NGF expression in the bladder reduces SCI-induced AD. Thus, Intravesical application of liposome-NGF antisense conjugates can be a new effective therapy for bladder distention-induced AD after SCI.

SUBMITTER: Kadekawa K

PROVIDER: S-EPMC5565153 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Project description:BackgroundTraumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI.MethodsA study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration.ResultsInitial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e., approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance.ConclusionsThe results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

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Effects of liposome-based local suppression of nerve growth factor in the bladder on autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury.

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