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Intranasal Delivery of Botulinum Neurotoxin A Protects against Hippocampal Neuron Death in the Lithium-Pilocarpine Rat Model

  • Zhi Huang
  • Yajun LianEmail author
  • Yuan Chen
  • Shuang Li
  • Haifeng Zhang
  • Nanchang Xie
  • Yake Zheng
  • Shouyi Wu
  • Yuhan Wang
  • Wenchao Cheng
  • Qiaoman Zhang
  • Chengze Wang
  • Yinping Shi
  • Na Xie
Original Paper

Abstract

Botulinum neurotoxins (BoNTs) block the release of a series of neurotransmitters, which are pivotal for neuron action. Intrahippocampal administration of BoNTs inhibits glutamate release, protects neurons against cell death, and attenuates epileptic seizures. Compared with intrahippocampal administration, intranasal delivery is less invasive and more practical for chronic drug administration. To assess whether intranasal administration is feasible, we examined the role of botulinum neurotoxin A (BoNT/A) in hippocampal neuronal injury after status epilepticus (SE) induced by pilocarpine. Our data showed BoNT/A could bypass the blood–brain barrier (BBB) and entered the olfactory bulb and hippocampal neurons. In addition, SE could result in up-regulation of pro-apoptotic proteins (Caspase-3, Bax), down-regulation of anti-apoptotic protein Bcl-2 and neuronal death in hippocampus. BoNT/A could suppress the expression of Caspase-3 and Bax, attenuate the decrease of Bcl-2, and inhibit hippocampal neuron death induced by SE. Meanwhile, there was no significant difference in cognitive behavior between the BoNT/A-pretreated rats and normal rats. Thus, we provided a more convenient and less invasive route for taking advantage of BoNT/A in the field of anti-epilepsy.

Keywords

Botulinum Neurotoxin A Intranasal delivery Epilepsy Olfactory nerve pathway Apoptosis 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81771397).

Compliance with Ethical Standards

Conflict of interest

No conflicts of interest

Supplementary material

11064_2019_2775_MOESM1_ESM.tif (4.1 mb)
The photos of native stained gels by coomassie blue staining (TIF 4193 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zhi Huang
    • 1
  • Yajun Lian
    • 1
    Email author
  • Yuan Chen
    • 1
  • Shuang Li
    • 1
  • Haifeng Zhang
    • 1
  • Nanchang Xie
    • 1
  • Yake Zheng
    • 1
  • Shouyi Wu
    • 1
  • Yuhan Wang
    • 1
  • Wenchao Cheng
    • 1
  • Qiaoman Zhang
    • 1
  • Chengze Wang
    • 1
  • Yinping Shi
    • 1
  • Na Xie
    • 2
  1. 1.Department of NeurologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouPeople’s Republic of China
  2. 2.Department of NeurologyAnyang Area HospitalAnyangPeople’s Republic of China

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