Mautes Angelika E M, Liu Jiankun, Brandewiede Jörg, Manville Jérôme, Snyder Evan, Schachner Melitta
Neurochirurgisches Forschungslabor Universität des Saarlandes, Homburg/Saar, Universität Hamburg, Germany.
J Mol Neurosci. 2004;24(2):227-36. doi: 10.1385/JMN:24:2:227.
Stem cells have been shown to partly restore central nervous system (CNS) function after transplantation into the injured CNS. However, little is known about their influence on acute energy metabolism after spinal cord injury. The present study was designed to analyze regional changes in energy metabolites. Young adult mice were subjected to laminectomy with subsequent hemisection at the L2/3 vertebral level. Immediately thereafter a stable clone of murine neural stem cells (NSCs) was injected into the lesion site. After 4 and 24 h, spinal cords were removed and ATP, glucose, and lactate were analyzed by a bioluminescence approach in serial sections and compared to a laminectomized (intact control), hemisected-only or hemisected vehicle-injected control group. At both time points, ATP content of the hemisected group in the tissue segments adjacent to the lesion was increased when compared to the laminectomized control. At the lesion site ATP content decreased significantly at 24 h in the cell-transplanted group when compared to the laminectomized control group. Glucose content decreased at the lesion site and in segments adjacent to the lesion at both time points and in all experimental groups when compared to the laminectomized control group. Lactate content decreased significantly at 4 h in the caudal segments of the vehicle-injected group and in both adjacent segments of the transplanted group when compared to the laminectomized control. At the lesion site, lactate content decreased significantly at 4 and 24 h in the cell-transplanted group, when compared to the laminectomized control. The area of ATP decline at the lesion site 24 h postinjury was significantly lower in the vehicle control group as compared to the hemisected or transplanted group. The decrease in glucose combined with an increase in ATP in the lesion-adjacent segments may indicate that the tissue responds with an increased use of glucose to support itself with sufficient ATP. The significant decrease in glucose, lactate, and ATP in the cell-transplanted group at 24 h may indicate a high metabolic need of the stem cells. The lower area of ATP decline 24 h after vehicle administration suggests that the vehicle solution washes out toxic mediators, thus ameliorating hemisection-dependent secondary tissue damage.
干细胞移植到受损的中枢神经系统后,已显示出能部分恢复中枢神经系统(CNS)功能。然而,关于它们对脊髓损伤后急性能量代谢的影响却知之甚少。本研究旨在分析能量代谢物的区域变化。对年轻成年小鼠进行椎板切除术,随后在L2/3椎体水平进行半横切。此后立即将稳定的小鼠神经干细胞(NSCs)克隆体注射到损伤部位。在4小时和24小时后,取出脊髓,通过生物发光法在连续切片中分析ATP、葡萄糖和乳酸,并与椎板切除(完整对照)、仅半横切或半横切后注射载体的对照组进行比较。在两个时间点,与椎板切除对照组相比,半横切组损伤部位相邻组织段的ATP含量均增加。与椎板切除对照组相比,细胞移植组在24小时时损伤部位的ATP含量显著降低。与椎板切除对照组相比,在两个时间点以及所有实验组中,损伤部位和损伤部位相邻段的葡萄糖含量均降低。与椎板切除对照组相比,注射载体组尾段以及移植组两个相邻段的乳酸含量在4小时时显著降低。在损伤部位,与椎板切除对照组相比,细胞移植组在4小时和24小时时的乳酸含量显著降低。损伤后24小时,载体对照组损伤部位ATP下降面积显著低于半横切组或移植组。损伤相邻段葡萄糖减少而ATP增加可能表明组织通过增加葡萄糖利用来以充足的ATP维持自身。细胞移植组在24小时时葡萄糖、乳酸和ATP的显著降低可能表明干细胞有很高的代谢需求。载体给药后24小时ATP下降面积较小表明载体溶液能清除毒性介质,从而减轻半横切依赖性继发性组织损伤。