Chinese Journal of Tissue Engineering Research ›› 2010, Vol. 14 ›› Issue (40): 7493-7496.doi: 10.3969/j.issn.1673-8225.2010.40.018

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N-methyl-D-aspartic acid receptor antagonist dose and proliferation of endogenous neural stem cells in the hippocampus of rats with cerebral ischemia/reperfusion

Ren Ming-xin 1,2, Zhou Li2, Li Na-na2, Feng Zhi-bo2, Zang Wei-dong1, Yuan Guo-yan3   

  1. 1 Department of Human Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou  450000, Henan Province, China; 2 Department of Human Anatomy, Xinxiang Medical University, Xinxiang  453003, Henan Province, China; 3 Department of Neurosurgery, First Affiliated Hospital, Xinxiang Medical University, Weihui  453100, Henan Province, China
  • Online:2010-10-01 Published:2010-10-01
  • Contact: Yuan Guo-yan, Master, Attending physician, Yuan Guo-yan, Master, Attending physician, Department of Neurosurgery, First Affiliated Hospital, Xinxiang Medical University, Weihui 453100, Henan Province, China hnlyrmx@163.com
  • About author:Ren Ming-xin★, Studying for master’s degree, Department of Human Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou 450000, Henan Province, China; Department of Human Anatomy, Xinxiang Medical University, Xinxiang 453003, Henan Province, China hnlyrmx@163.com
  • Supported by:

    the Seventh Batch Provincial-level Key Subject Opening Topic of Xinxiang Medical University in 2009, No. ZD200923*

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Abstract:

BACKGROUND: After cerebral ischemia-reperfusion, excessive excitatory amino acids activate N-methyl-D-aspartic acid (NMDA) receptor which repairs nerve cells by the proliferation and differentiation of endogenous neural stem cells (NSCs), but damages nerve cells by intracellular calcium overload at the same time. Controlling NMDA receptor activation may activate endogenous NSCs and minimize damage simultaneously.
OBJECTIVE: To investigate the effect of NMDA receptor antagonist MK-801 on endogenous neural stem cell proliferation of reperfused rat hippocampus.
METHODS: A total of 54 healthy male Sprague-Dawley rats were randomized into control group (without any treatment), operation group (establish ischemia model), various doses of MK-801 group. Four-vessel occlusion (Pulsinelli-4VO method) was used to establish global cerebral ischemia/reperfusion model. Different doses of MK-801 were injected into lateral ventricle 30 minutes before cerebral ischemia according to 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg/kg. Western-blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect nestin protein and mRNA level expression in each group.
RESULTS AND CONCLUDION: When MK-801 was under 0.8 mg/kg, no significant differences in the protein and mRNA expression of nestin were detected among groups (P > 0.05), with the presence of high expression. When MK-801 was equal to 0.8 mg/kg, MK-801 significantly suppressed proliferation of endogenous NSCs. When MK-801 was more than 0.8 mg/kg, inhibitory effect was increased with increased concentration. At 1.2 mg/kg, rats developed adverse reaction such as restlessness and ataxia. The nestin mRNA expression results were consistent with the tendency of protein expression, which suggested that MK-801 dose is associated with the repair of nerve function following cerebral infarction. 0.6 mg/kg is a suitable dose during this test. This concentration can make MK-801 reduce the toxic effect of excitatory amino acids on neurons, can protect neural cells, and cannot greatly affect proliferation of endogenous NSCs.

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