Abstract
Objective
To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury.
Methods
Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum (dpc). The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG+NSCs group received intracerebroventricular transplantation of NSCs (approximately 1.0×105 cells) separately on day 1 and day 10 after 10-d MSG exposure (4.0 g/kg per day). The mice in control and MSG groups received intracerebroventricular injection of Dulbecco’s minimum essential medium (DMEM) instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair.
Results
The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice.
Conclusion
Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.
摘要
目的
探讨脑室内神经干细胞移植修复成年小鼠谷氨酸神经毒性损伤的可能性。
方法
从15日小鼠胚胎脑组织分离神经干细胞?采用免疫细胞化学技术检测细胞 Nestin 抗原表达; 通过免疫荧光染色观察所移植神经干细胞在体内的存活及定位。 除对照组外, 所有小鼠均以谷氨酸单钠(每天4.0 g/kg)灌胃, 连续10 天。 灌胃后第 1 天和 10 天, 谷氨酸加神经干细胞移植组行神经干细胞脑室内移植(1 × 105 细胞/鼠), 对照组和谷氨酸组注射 DMEM 液。 末次移植后第 11 天进行 Y 迷宫试验, 试验结束后进行小鼠脑病理检查, 以分析谷氨酸引起的脑功能和形态学上的改变。
结果
所分离细胞呈 Nestin 阳性表达; 移植 10 天后所移植神经干细胞在小鼠脑中呈区域特异性存活; 脑室内移植神经干细胞能明显促进成年小鼠脑谷氨酸兴奋性毒性损伤的修复。
结论
脑室内移植神经干细胞可用于疾病或损伤脑组织的修复。
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Lipton SA, Rosenberg RA. Mechanisms of disease: excitatory amino acids as a final common pathway in neurologic disorders. N Engl J Med 1994, 330: 613–622.
Yu TX, Zhao Y, Shi WC, Ma RD, Yu LJ. Effects of maternal oral administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Brain Res 1997, 747: 195–206.
Yu LJ, Zhang YP, Ma RD, Bao L, Fang JZ, Yu TX. Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Eur Neuropsychopharmacol 2006, 16: 170–177.
Corti S, Locatelli F, Strazzer S, Guglieri M, Comi GP. Neuronal generation from somatic stem cells: current knowledge and perspectives on the treatment of acquired and degenerative central nervous system disorders. Curr Gene Ther 2003, 3: 247–272.
Wennersten A, Meier X, Holmin S, Wahlberg L, Mathiesen T. Proliferation, migration, and differentiation of human neural stem/progenitor cells after transplantation into a rat model of traumatic brain injury. J Neurosurg 2004, 100: 88–96.
Wachs FP, Couillard-Despres S, Engelhardt M, Wilhelm D, Ploetz S, Vroemen M, et al. High efficacy of clonal growth and expansion of adult neural stem cells. Lab Invest 2003, 83: 949–962.
Ourednik V, Ourednik J, Park KI, Teng YD, Aboody KA, Auguste KI, et al. Neural stem cells are uniquely suited for cell replacement and gene therapy in the CNS. Novartis Found Symp 2000, 231: 242–269; 302–306.
Park KI, Himes BT, Stieg PE, Tessler A, Fischer I, Snyd EY. Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury. Exp Neurol 2006, 199:179–190.
Podhorna J, Brown RE. Strain differences in activity and emotionality do not account for differences in learning and memory performance between C57BL/6 and DBA/2 mice. Gen Brain Behav 2002, 1: 96–110.
Xu BH, Duan HF, Liu RY. The effect on learing and memory of application of RNAase to hippocampus of rats. Chin Sci Bull 1979, 24: 182–185.
Lu WG, Chen H, Wang D, Li FG, Zhang SM. Regionspecific survival and differentiation of mouse embryonic stem cellderived implants in the adult rat brain. Acta Physiol Sin 2007, 59: 51–57.
Tao KX, Chen JB, Wang GB, Shu XG. Culture and Identification of Monoclonal Neural Stem Cells Derived from Cerebral Cortex. J Huazhong Univ Sci Tech (Med Sci) 2006, 26: 451–454.
Limbrick DD Jr, Sombati S, DeLorenzo RJ. Calcium influx constitutes the ionic basis for the maintenance of glutamateinduced extended neuronal depolarization associated with hippocampal neuronal death. Cell Calcium 2003, 33: 69–81.
Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, et al. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci USA 1995, 92: 11879–11883.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Ma, J., Yu, LJ., Ma, RD. et al. Repair of glutamate-induced excitotoxic neuronal damage mediated by intracerebroventricular transplantation of neural stem cells in adult mice. Neurosci. Bull. 23, 209–214 (2007). https://doi.org/10.1007/s12264-007-0031-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12264-007-0031-0