Munoz Alvaro
Regenerative Medicine and Tissue Engineering Program, Houston Methodist Research Institute, and Department of Urology, Houston Methodist Hospital, Houston, TX, 77030, United States.
Brain Res Bull. 2017 May;131:18-24. doi: 10.1016/j.brainresbull.2017.02.010. Epub 2017 Mar 3.
Rodent models for the study of neurogenic bladder dysfunction after spinal cord injury (SCI) are difficult to standardize, particularly when evaluating the specific contribution of the SCI to end-organ function. The purpose of this study was to evaluate the degree of bladder dysfunction associated with a highly reproducible, contusion-induced SCI in female rats. An infinite horizon impactor was used to create a contusion SCI with a magnitude of either 100 or 150 kDyne at the T8/T9 thoracic region of female Sprague-Dawley rats. Locomotor function, and the presence of astrocytes (positive regions for Glial Fibrillary Acidic Protein) and microglia (positive cells for the integrin CD11b) at the SCI site were determined at four weeks after SCI. Similarly, cystometric properties were characterized in urethane anesthetized rats at four weeks post-SCI. The significant increases in astrocyte and microglia in the T8/T9 region in all of the SCI animals did not correlate with locomotor impairment or bladder dysfunction. After performing the cystometric studies substantial differences were found in both SCI groups when compared to intact animals, specifically a high frequency of non-voiding contractions, different durations for intraluminal pressure-high frequency oscillations, intercontractile intervals, impaired micturition volumes, and estimated voiding efficiency. These results suggest that a contusion SCI can increase microglia and astrocyte activation without a strong association with bladder dysfunction. The present study will be important for precise considerations about correlating the intensity of an SCI with impairment outcomes at both locomotor or organ function levels.
用于研究脊髓损伤(SCI)后神经源性膀胱功能障碍的啮齿动物模型难以标准化,尤其是在评估SCI对终末器官功能的具体影响时。本研究的目的是评估雌性大鼠中与高度可重复的挫伤性SCI相关的膀胱功能障碍程度。使用无限视野撞击器在雌性Sprague-Dawley大鼠的T8/T9胸椎区域造成100或150达因的挫伤性SCI。在SCI后四周测定运动功能,以及SCI部位星形胶质细胞(胶质纤维酸性蛋白阳性区域)和小胶质细胞(整合素CD11b阳性细胞)的存在情况。同样,在SCI后四周对经乌拉坦麻醉的大鼠进行膀胱测压特性分析。所有SCI动物T8/T9区域星形胶质细胞和小胶质细胞的显著增加与运动功能障碍或膀胱功能障碍无关。在进行膀胱测压研究后,与完整动物相比,两个SCI组均发现了显著差异,具体表现为无排尿收缩频率高、腔内压力高频振荡持续时间不同、收缩间期不同、排尿量受损以及估计排尿效率。这些结果表明,挫伤性SCI可增加小胶质细胞和星形胶质细胞的激活,但与膀胱功能障碍无强烈关联。本研究对于精确考虑SCI强度与运动或器官功能水平的损伤结果之间的相关性具有重要意义。