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  4. Growth‑Promoting Treatment Screening for Corticospinal Neurons in Mouse and Man

Growth‑Promoting Treatment Screening for Corticospinal Neurons in Mouse and Man

Cellular and Molecular Neurobiology, 2020 · DOI: 10.1007/s10571-020-00820-7 · Published: March 14, 2020

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

The corticospinal tract (CST) is particularly notorious for its poor regeneration. Here, we developed a tissue culture model for CST regeneration and found that IL-4 promoted new growth cone formation after axon transection. Overall, these findings serve as proof-of-concept that our CST regeneration model is suitable for fast screening of new treatments for SCI.

Study Duration
Not specified
Participants
Mice and human neural stem cells
Evidence Level
Not specified

Key Findings

  • 1
    IL-4 promoted new growth cone formation after axon transection.
  • 2
    IL-4 directly increased the regenerative capacity of both murine and human CST axons, which corroborates its regenerative effects in CNS damage.
  • 3
    IL-4 is able to directly stimulate CST neurite outgrowth and regeneration of mouse CxV explants and human CST neurons.

Research Summary

Here, we developed a tissue culture model for CST regeneration and found that IL-4 promoted new growth cone formation after axon transection. Most importantly, IL-4 directly increased the regenerative capacity of both murine and human CST axons, which corroborates its regenerative effects in CNS damage. Overall, these findings serve as proof-of-concept that our CST regeneration model is suitable for fast screening of new treatments for SCI.

Practical Implications

Treatment Screening

The CST regeneration model is suitable for fast screening of new treatments for SCI.

Therapeutic Target

Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation.

Clinical Translation

The ability to test growth-promoting treatments on human neurons is a significant step forward in the regeneration field.

Study Limitations

  • 1
    CxV cultures displayed high expression of PTEN and SOCS3, which are known limiting factors in CNS regeneration.
  • 2
    CxV cultures have a limited growth capacity, allowing stimulation by putative growth-promoting treatments.
  • 3
    Mouse IL-4 is unable to bind and stimulate the human IL-4R at physiological concentrations.

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