Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice.
Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice.
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DOI：
10.1371/journal.pone.0139335
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lee YS
中科院分区：
文献类型：
--
作者：
DePaul MA;Lin CY;Silver J;Lee YS
下尿路（LUT）控制的丧失是完全性脊髓损伤的普遍后果，归因于控制膀胱的椎管上通路缺乏再生。我们实验室之前的工作利用周围神经自体移植物（PNG）、酸性成纤维细胞生长因子（aFGF）和软骨素酶ABC （ChABC）联合治疗成年大鼠的T8脊髓完全横断，导致脊髓上膀胱功能的控制。在本研究中，我们通过检验在T8横断小鼠模型中使用PNG+aFGF+ChABC组合治疗来扩展这些发现，T8横断小鼠模型更接近于脊髓损伤后人类尿缺陷的模型。膀胱术分析和外尿道括约肌肌电图显示，PNG+aFGF+ChABC治疗膀胱重量减轻，膀胱和外尿道括约肌组织学改善，LUT功能明显增强，排尿效率提高。经治疗的小鼠脊髓损伤也显示胶原蛋白瘢痕减少，5 -羟色胺能和酪氨酸羟化酶阳性轴突在损伤处再生，并进入脊髓远端。5 -羟色胺轴突再生与LUT恢复相关。这些结果表明，我们的小鼠LUT功能障碍模型概括了在大鼠模型中发现的结果，并可用于进一步研究基因对再生失败的贡献。
The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a complete spinal cord injury, attributed to a lack of regeneration of supraspinal pathways controlling the bladder. Previous work in our lab has utilized a combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8 spinal cord transection in the adult rat, resulting in supraspinal control of bladder function. In the present study we extended these findings by examining the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse model, which more closely models human urinary deficits following spinal cord injury. Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding. Treated mice’s injured spinal cord also showed a reduction in collagen scaring, and regeneration of serotonergic and tyrosine hydroxylase-positive axons across the lesion and into the distal spinal cord. Regeneration of serotonin axons correlated with LUT recovery. These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.