In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.

中文翻译：

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重度先天性阻塞性脑积水在脑室内施用骨髓源性间充质干细胞后，新皮质组织恢复。

在阻塞性先天性脑积水中，脑脊液积聚与颅内压高，脑室周围水肿，局部缺血/缺氧，白质损伤和新皮质的神经胶质反应有关。在hyh小鼠模型的这种病理条件下，已经评估了基于骨髓间充质干细胞（BM-MSC）的疗法的生存力和短期效果。从表达荧光性mRFP1蛋白的小鼠获得的BM-MSC在出现严重疾病时被注射到脑积水hyh小鼠的侧脑室。将新皮质中移植的效果与注射了媒介物和非脑积水同窝仔的脑积水hyh小鼠进行了比较。分析了神经细胞群体和转分化的可能性。使用1H高分辨率魔角旋转核磁共振（1H HR-MAS NMR）光谱研究了组织恢复的可能性，从而可以检测与脑积水严重程度和新皮层结局相关的代谢物/渗透物。使用BM-MSC在高TNFα水平条件下进行了体外试验，以模拟心室周围星形胶质细胞反应条件。在该测定中分析了培养基中的分泌组。移植后四天，发现BM-MSC未分化并散布到受损的新皮层白质中存在的星形胶质细胞反应中。移植后4天未检测到对整合的BM-MSC的组织排斥。移植BM-MSC的Hyh小鼠的脑室周围新皮质壁细胞凋亡减少，提示在这些情况下BM-MSC的神经保护作用。新皮层中诸如牛磺酸和神经外毒素谷氨酸的代谢物/渗透物水平的降低也表明组织正在恢复。在高TNFα水平的体外条件下，BM-MSC上调了细胞因子和蛋白质分泌，这可能解释了归巢，免疫调节和血管通透性，从而恢复了组织。在严重的先天性脑积水中进行BM-MSC治疗是可行的，并可导致新皮层中严重的神经退行性疾病的恢复。核磁共振波谱法可以追踪脑积水中干细胞治疗的效果。还表明组织正在恢复。在高TNFα水平的体外条件下，BM-MSC上调了细胞因子和蛋白质分泌，这可能解释了归巢，免疫调节和血管通透性，从而恢复了组织。在严重的先天性脑积水中进行BM-MSC治疗是可行的，并可导致新皮层中严重的神经退行性疾病的恢复。核磁共振波谱法可以追踪脑积水中干细胞治疗的效果。还表明组织正在恢复。在高TNFα水平的体外条件下，BM-MSC上调了细胞因子和蛋白质分泌，这可能解释了归巢，免疫调节和血管通透性，从而恢复了组织。在严重的先天性脑积水中进行BM-MSC治疗是可行的，并可导致新皮层中严重的神经退行性疾病的恢复。核磁共振波谱法可以追踪脑积水中干细胞治疗的效果。