A Sensitized IGF1 Treatment Restores Corticospinal Axon-Dependent Functions

Yuanyuan Liu, Xuhua Wang, Wenlei Li, Qian Zhang, Yi Li, Zicong Zhang, Junjie Zhu, Bo Chen, Philip R. Williams, Yiming Zhang, Bin Yu, Xiaosong Gu, Zhigang He

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

A major hurdle for functional recovery after both spinal cord injury and cortical stroke is the limited regrowth of the axons in the corticospinal tract (CST) that originate in the motor cortex and innervate the spinal cord. Despite recent advances in engaging the intrinsic mechanisms that control CST regrowth, it remains to be tested whether such methods can promote functional recovery in translatable settings. Here we show that post-lesional AAV-assisted co-expression of two soluble proteins, namely insulin-like growth factor 1 (IGF1) and osteopontin (OPN), in cortical neurons leads to robust CST regrowth and the recovery of CST-dependent behavioral performance after both T10 lateral spinal hemisection and a unilateral cortical stroke. In these mice, a compound able to increase axon conduction, 4-aminopyridine-3-methanol, promotes further improvement in CST-dependent behavioral tasks. Thus, our results demonstrate a potentially translatable strategy for restoring cortical dependent function after injury in the adult.

Original languageEnglish (US)
Pages (from-to)817-833.e4
JournalNeuron
Volume95
Issue number4
DOIs
StatePublished - Aug 16 2017

Keywords

  • 4-aminopyridine
  • IGF1
  • axon regeneration
  • axon sprouting
  • ischemic stroke
  • osteopontin
  • spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)

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    Liu, Y., Wang, X., Li, W., Zhang, Q., Li, Y., Zhang, Z., Zhu, J., Chen, B., Williams, P. R., Zhang, Y., Yu, B., Gu, X., & He, Z. (2017). A Sensitized IGF1 Treatment Restores Corticospinal Axon-Dependent Functions. Neuron, 95(4), 817-833.e4. https://doi.org/10.1016/j.neuron.2017.07.037