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Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2008 Feb 1;23(4):209–214. doi: 10.1007/s12264-007-0031-0

Repair of glutamate-induced excitotoxic neuronal damage mediated by intracerebroventricular transplantation of neural stem cells in adult mice

脑室内神经干细胞移植修复谷氨酸导致的成年小鼠神经损伤

Juan Ma 1, Li-Jian Yu 1,, Run-Di Ma 1, Yong-Ping Zhang 1, Juan-Zhi Fang 1, Xiao-Yu Zhang 1, Ting-Xi Yu 1,
PMCID: PMC5550583  PMID: 17687395

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.

Keywords: brain repair, neural stem cells, transplantation, excitotoxic injury, mice

Contributor Information

Li-Jian Yu, Phone: 86-759-2382041, FAX: 86-759-2382424, Email: ywyj9578@sohu.com.

Ting-Xi Yu, Email: yutingxi@yahoo.com.

References

  • [1].Lipton S.A., Rosenberg R.A. Mechanisms of disease: excitatory amino acids as a final common pathway in neurologic disorders. N Engl J Med. 1994;330:613–622. doi: 10.1056/NEJM199403033300907. [DOI] [PubMed] [Google Scholar]
  • [2].Yu T.X., Zhao Y., Shi W.C., Ma R.D., Yu L.J. 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. doi: 10.1016/S0006-8993(96)01181-X. [DOI] [PubMed] [Google Scholar]
  • [3].Yu L.J., Zhang Y.P., Ma R.D., Bao L., Fang J.Z., Yu T.X. 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. doi: 10.1016/j.euroneuro.2005.08.006. [DOI] [PubMed] [Google Scholar]
  • [4].Corti S., Locatelli F., Strazzer S., Guglieri M., Comi G.P. 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. doi: 10.2174/1566523034578375. [DOI] [PubMed] [Google Scholar]
  • [5].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. doi: 10.3171/jns.2004.100.1.0088. [DOI] [PubMed] [Google Scholar]
  • [6].Wachs F.P., 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. doi: 10.1097/01.LAB.0000075556.74231.A5. [DOI] [PubMed] [Google Scholar]
  • [7].Ourednik V., Ourednik J., Park K.I., Teng Y.D., Aboody K.A., Auguste K.I., et al. Neural stem cells are uniquely suited for cell replacement and gene therapy in the CNS. Novartis Found Symp. 2000;231:242–269. doi: 10.1002/0470870834.ch15. [DOI] [PubMed] [Google Scholar]
  • [8].Park K.I., Himes B.T., Stieg P.E., Tessler A., Fischer I., Snyd E.Y. 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. doi: 10.1016/j.expneurol.2006.03.016. [DOI] [PubMed] [Google Scholar]
  • [9].Podhorna J., Brown R.E. 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. doi: 10.1034/j.1601-183X.2002.10205.x. [DOI] [PubMed] [Google Scholar]
  • [10].Xu B.H., Duan H.F., Liu R.Y. The effect on learing and memory of application of RNAase to hippocampus of rats. Chin Sci Bull. 1979;24:182–185. [Google Scholar]
  • [11].Lu W.G., Chen H., Wang D., Li F.G., Zhang S.M. Regionspecific survival and differentiation of mouse embryonic stem cellderived implants in the adult rat brain. Acta Physiol Sin. 2007;59:51–57. [PubMed] [Google Scholar]
  • [12].Tao K.X., Chen J.B., Wang G.B., Shu X.G. Culture and Identification of Monoclonal Neural Stem Cells Derived from Cerebral Cortex. J Huazhong Univ Sci Tech (Med Sci) 2006;26:451–454. doi: 10.1007/s11596-006-0419-5. [DOI] [PubMed] [Google Scholar]
  • [13].Limbrick D.D., Jr, Sombati S., DeLorenzo R.J. 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. doi: 10.1016/S0143-4160(02)00054-4. [DOI] [PubMed] [Google Scholar]
  • [14].Gage F.H., Coates P.W., Palmer T.D., Kuhn H.G., Fisher L.J., Suhonen J.O., et al. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci USA. 1995;92:11879–11883. doi: 10.1073/pnas.92.25.11879. [DOI] [PMC free article] [PubMed] [Google Scholar]

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