Epac2 Promotes Axonal Outgrowth and Attenuates the Glial Reaction in an Ex Vivo Model of Spinal Cord Injury

AbstractVolume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.

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Alterations of the ex vivo biomechanical properties of the female rat urethra in Spinal Cord Injury (SCI) and Stress Urinary Incontinence (SUI)

Journal of Biomechanics ◽

10.1016/s0021-9290(06)84576-8 ◽

2006 ◽

Vol 39 ◽

pp. S390

Author(s):

R. Prantil ◽

M. Chancellor ◽

N. Yoshimura ◽

W. de Groat ◽

D. Vorp

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Urinary Incontinence ◽

Stress Urinary Incontinence ◽

Ex Vivo ◽

Biomechanical Properties ◽

Female Rat ◽

Cord Injury

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MULTIMODAL NONLINEAR OPTICAL IMAGING OF CELL–MATRIX INTERACTION DURING SPINAL CORD INJURY EX VIVO

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237211002554 ◽

2011 ◽

Vol 23 (03) ◽

pp. 223-230 ◽

Cited By ~ 1

Author(s):

Yi-Cheng Huang ◽

Te-Hsuen Chen ◽

Wen-Chun Kuo ◽

Sung-Hao Hsu ◽

Yi-You Huang ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Ex Vivo ◽

Second Harmonic ◽

Two Photon ◽

Matrix Interaction ◽

Cell Matrix ◽

Photon Excitation ◽

Cord Injury ◽

Near Future

Neurons within spinal cord injury (SCI) are prevented from regeneration because of scar formation. Chondroitinase ABC (ChABC) was reported to promote functional recovery after spinal cord injury. However, the mechanism and the role of ChABC in the recovery are not clear. In this research, we used second harmonic generation (SHG) and two-photon excitation fluorescence (2PEF) images as probes to observe cell–matrix interaction on fibrosis after SCI followed by ChABC treatment. According to our experimental results, the enzyme ChABC could decrease cystic formation dramatically and consequently allow the spinal cord to regenerate. Using immunohistological analysis, we found that treatment with ChABC at the lesion area resulted in fewer chondroitin sulfate proteoglycans (CSPGs) remaining, longer axonal re-growth, and more new developmental neurons. Furthermore, ChABC 1 U/ml was more effective than 5 U/ml treatment. Using the noninvasive technology, SHG and 2PEF images, we could observe cell–matrix interaction clearly, not only in fixed samples but also in unfixed ex vivo samples. This technology presents a potential for clinical use in the near future.

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