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Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

ABSTRACT: Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine?associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography?mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine?treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed.

SUBMITTER: Shen CH

PROVIDER: S-EPMC4991691 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

Shen Cheng-Huang CH Wang Shou-Chieh SC Wang Shou-Tsung ST Lin Shu-Mei SM Wu Jiann-Der JD Lin Chang-Te CT Liu Yi-Wen YW

Molecular medicine reports 20160707 3

Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine‑associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine h ...[more]

PMID: 27431428

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Project description:To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies including urinary diversion and bladder augmentation enterocystoplasty (BAE) utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist which need to be overcome in order to advance tissue engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utlity of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of appropriate animal model for testing. Here we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold co-seeded with autologous bone marrow-derived mesenchymal stem cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs) supports robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem cell-seeded small intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem cell synergism promoted functional tri-layer bladder tissue regeneration including whole graft neurovascularization in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

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Dataset Information

Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

Publications

Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

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