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Chinese Journal of Neurotraumatic Surgery(Electronic Edition) ›› 2020, Vol. 06 ›› Issue (05): 292-298. doi: 10.3877/cma.j.issn.2095-9141.2020.05.009

Special Issue:

• Basic Research • Previous Articles     Next Articles

Study on the therapeutic effect of anti-tau antibody gene therapy on chronic traumatic encephalopathy

Cijing Chai1, Yue Tu2, Qicai Zhang2, Yiling Hou1,()   

  1. 1. Physical Examination Center of Armed Police Medical Center, Tianjin 300162, China
    2. Institute of Traumatic Brain Trauma and Neurology of Armed Police Medical Center, Tianjin 300162, China
  • Received:2020-06-20 Online:2020-10-15 Published:2020-10-15
  • Contact: Yiling Hou
  • About author:
    Corresponding author: Hou Yiling, Email:

Abstract:

Objective

To investigate the direct intervention of anti-tau protein (pTau) gene adeno-associated virus (AAV) vector in the treatment of chronic traumatic encephalopathy (CTE).

Methods

Twenty-four C57 mice were randomly divided into three groups (n=8), normal control group (sham group), CTE 4 weeks group and CTE 12 weeks group. The CTE mice model was established by cortical impact method. The relative level of pTau protein in brain tissue was detected by Western blot at the 4th and 12th week of the experiment. The remaining 56 mice were randomly divided into 7 groups (n=8): sham group, noAAV group, AAVrh.10Null group and vector group encoding 2B6, CisTau, IPN007 and PHF1 gene vectors. Except for sham group, CTE models were established by cortical impact method. At the 3rd week, the sham group and noAAV group were injected with the same amount of artificial cerebrospinal fluid. The other groups of mice were injected with the corresponding gene encoding expression vector in the hippocampus. At the 4th week, all mice were euthanized. The expression of anti pTau antibody in brain tissue was evaluated by immunofluorescence and Western blot, and the therapeutic effect on CTE mice was also evaluated.

Results

pTau in CTE mice in the 4 and 12 weeks groups was significantly higher than that in sham group, and the difference were statistically significant (P<0.05). Aavrh.10PHF1 and AAVrh.10IPN treatment group significantly reduced the level of pTau in mouse brain tissue, and aAVRh.10PHF1 group was superior to AAVrh.10IPN group (P=0.032).

Conclusion

Direct treatment of AAVrh.10 virus vector CNS with anti-pTau antibody gene is effective and provides a new direction for the treatment of CTE.

Key words: Chronic traumatic encephalopathy, Entral nervous system, Adeno-associated virus, Tau protein

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