Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury

Cell Death and Disease, 2013 · DOI: 10.1038/cddis.2013.102 · Published: April 4, 2013

Regenerative Medicine Neurology Brain Injury

Simple Explanation

Brain injuries often lead to motor deficits, and the brain's ability to reorganize neural connections is crucial for regaining lost function. However, this ability is limited in adults. This study investigates whether inhibiting a protein called SHP-1 can enhance the brain's capacity to reorganize and recover after injury. The study uses mice with a genetic deficiency in SHP-1 and wild-type mice treated with an SHP-1 inhibitor to examine corticospinal tract (CST) sprouting after a cortical injury. The CST is a major pathway for motor control, and its reorganization can contribute to functional recovery. The researchers found that suppressing SHP-1 activity promoted CST sprouting and improved motor function recovery after brain injury. This suggests that SHP-1 inhibition could be a potential therapeutic strategy for promoting brain repair after injury.

Study Duration

4 weeks

Participants

Wild-type and SHP-1-deficient heterozygous viable motheaten mice

Evidence Level

Not specified

Key Findings

1
SHP-1 expression and activity increase in the contralesional cortex (the side opposite the injury) after a unilateral motor cortex injury.
2
Mice with reduced SHP-1 activity (SHP-1-deficient heterozygous viable motheaten mice) show increased sprouting of corticospinal axons into the denervated side of the cervical spinal cord after injury.
3
Motor function recovery of the impaired forelimb is enhanced in SHP-1-deficient mice.

Research Summary

This study investigates the role of SHP-1, an intracellular protein tyrosine phosphatase, in axonal reorganization and functional recovery after brain injury. The researchers hypothesized that SHP-1 negatively affects axonal plasticity and tested this by examining corticospinal tract (CST) sprouting in mice with reduced SHP-1 activity. The results showed that unilateral motor cortex injury leads to increased expression and activity of SHP-1 in the contralesional cortex. Furthermore, SHP-1 deficiency or inhibition promotes CST sprouting into the denervated side of the cervical spinal cord and enhances motor function recovery. The findings suggest that downregulation of SHP-1 activity could be a potential therapeutic strategy for promoting axonal plasticity and functional recovery after brain injury. This is because SHP-1 suppression enhances signals that induce axonal regeneration.

Practical Implications

Therapeutic Target

SHP-1 could be a potential therapeutic target for promoting axonal plasticity and functional recovery after brain injury.

Drug Development

Development of SHP-1 inhibitors could offer a new avenue for treating brain injuries and promoting neural repair.

Combination Therapies

Combining SHP-1 inhibition with other rehabilitation strategies could enhance functional outcomes after brain injury.

Study Limitations

1
The study used a murine model of cortical injury, and the results may not directly translate to humans.
2
The genetic approach used heterozygous mev mice due to the shortened lifespan of homozygous mev mice, which may have influenced the results.
3
The study focused primarily on CST sprouting, and the role of other neural pathways in functional recovery was not fully explored.

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