Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America.
PLoS One. 2012;7(8):e42845. doi: 10.1371/journal.pone.0042845. Epub 2012 Aug 10.
Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests. Significant correlations were detected between MRI ventricular volumes and histological lesion volume as well as number of apoptotic cells. A positive correlation was also observed between MRI CBF or cerebral blood volume (CBV) and histological synaptic density. Neurological functional tests were also significantly correlated with MRI ventricular volume and CBV. Our data demonstrated that MRI measurements can detect the effect of hUTC therapy on the brain reorganization and exhibited positive correlation with histological measurements of brain structural changes and functional behavioral tests after stroke. MRI ventricular volumes provided the most sensitive index in monitoring brain remodeling and treatment effects and highly correlated with histological and functional measurements.
人脐带组织来源的细胞(hUTC)是一种有吸引力的细胞来源,也是神经修复和改善中风后功能结果的潜在技术。雄性 Wistar 大鼠接受短暂性大脑中动脉闭塞(tMCAo),中风后 48 小时静脉给予 hUTC(N=11)或载体(N=10)。使用 MRI 和组织病理学监测 12 周内的白质和血管重组。MRI 结果与神经功能和组织学结果相关联,以证明 MRI 可以作为测量中风后结构恢复的有用工具。MRI 显示 hUTC 治疗组与载体治疗组相比,脑室容积扩张显著减少,脑血流(CBF)改善。hUTC 治疗导致组织学和功能改善,表现为 vWF 和突触素表达增强,以及行为测试结果改善。在 MRI 脑室容积和组织学病变容积以及凋亡细胞数量之间检测到显著相关性。MRI CBF 或脑血容量(CBV)与组织学突触密度之间也观察到正相关。神经功能测试也与 MRI 脑室容积和 CBV 显著相关。我们的数据表明,MRI 测量可以检测 hUTC 治疗对大脑重组的影响,并与中风后大脑结构变化和功能行为测试的组织学测量呈正相关。MRI 脑室容积提供了监测脑重塑和治疗效果的最敏感指标,与组织学和功能测量高度相关。