Inositol Polyphosphate-5-Phosphatase K (Inpp5k) Enhances Sprouting of Corticospinal Tract Axons after CNS Trauma

The Journal of Neuroscience, 2022 · DOI: https://doi.org/10.1523/JNEUROSCI.0897-21.2022 · Published: March 16, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how to stimulate nerve fiber regrowth after spinal cord injury, which often leads to permanent disabilities. Researchers looked for genes that promote axon growth in adult corticospinal neurons, which control voluntary movement. They found that a gene called Inpp5k, which is involved in a specific cellular pathway, can enhance the sprouting of these nerve fibers after injuries like spinal cord injury and stroke in mice. The research suggests that targeting Inpp5k could be a new way to encourage nerve repair and improve recovery after CNS trauma, although further research is needed to translate these findings into clinical treatments.

Study Duration

Not specified

Participants

Male and female C57BL/6 mice

Evidence Level

Level II; Preclinical animal study

Key Findings

1
Inpp5k increases axon outgrowth of cortical neurons in vitro by increasing the availability of active nonphosphorylated cofilin within labile axonal growth cones.
2
Overexpression of Inpp5k enhances the plasticity of intact CSNs after pyramidotomy and cortical stroke.
3
Inpp5k increases the sprouting of CSNs rostral to acute severe thoracic contusion SCI and after chronic contusion injury but does not increase the regeneration of damaged CSNs after SCI.

Research Summary

This study aimed to identify novel axon growth activators induced in the adult CNS environment in vivo, focusing on Inpp5k's role in enhancing corticospinal tract (CST) axon growth after CNS trauma. The researchers found that Inpp5k overexpression in intact adult CSNs in mice enhanced CST terminal sprouting after pyramidotomy and cortical stroke, and CST axon sprouting after acute and chronic spinal contusion. The study concludes that Inpp5k is a novel CST growth activator, validating in vivo transcriptional screening as a method for identifying cell-autonomous factors capable of repairing the damaged CNS.

Practical Implications

Therapeutic Target

Inpp5k is a potential therapeutic target for promoting axon growth and plasticity in CNS injuries, like stroke and spinal cord injury.

Drug Development

Development of drugs that modulate Inpp5k activity could enhance nerve repair and improve functional outcomes after CNS trauma.

Personalized Medicine

Understanding the specific molecular profiles of CSN subtypes could lead to more targeted and effective therapeutic interventions for spinal cord injuries, focusing on specific regions of the spinal cord, for instance targeting lumbar CSNs after thoracic SCI.

Study Limitations

1
Grid-walking analysis may not have been sensitive enough to detect small but important functional gains associated with increased compensatory CST sprouting.
2
The study could not determine whether the sprouting axons were intact cervical CST axons or axotomized lumbar axons.
3
The homogeneity of CSNs is questionable, potentially limiting generalizability.

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