Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

PNAS, 2003 · DOI: 10.1073/pnas.1533187100 · Published: July 22, 2003

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The adult mammalian spinal cord's failure to regenerate axons after injury results in permanent functional impairments. This is largely due to an inhospitable environment caused by an astrocytic scar. Mice lacking glial fibrillary acidic protein and vimentin, the major proteins of the astrocyte cytoskeleton, showed reduced astroglial reactivity after spinal cord hemisection. These mice also displayed increased plastic sprouting of supraspinal axons, including the reconstruction of circuits that led to functional restoration.

Study Duration

5 weeks

Participants

100 adult female mice

Evidence Level

Animal study

Key Findings

1
Double mutant mice (lacking both GFAP and Vimentin) exhibited significant recovery of locomotor function 5 weeks after spinal cord hemisection.
2
The functional recovery in double mutant mice correlated with reduced glial reactivity in the lesioned side of the spinal cord, compared to wild-type and single mutant mice.
3
Double mutant mice showed extensive plastic sprouting of both serotonergic raphespinal and corticospinal pathways below the lesion level.

Research Summary

This study investigates the impact of glial fibrillary acidic protein (GFAP) and vimentin deficiency on axonal plasticity and functional recovery following spinal cord injury (SCI) in mice. The key finding is that mice lacking both GFAP and vimentin exhibit improved locomotor function recovery, reduced astroglial reactivity, and increased axonal sprouting compared to wild-type and single-mutant mice. The absence of both proteins modifies the morphological features of reactive astrocytes by abolishing or reducing the physical glial barrier essentially made by their tightly interlinked hypertrophic processes.

Practical Implications

Therapeutic Target Identification

Reactive astrocytes, specifically the proteins GFAP and Vimentin, are potential therapeutic targets for promoting axonal regeneration and functional recovery after CNS injuries.

Drug Development

Developing drugs that can modulate the activity or expression of GFAP and Vimentin in astrocytes could improve outcomes after spinal cord injury.

Understanding CNS Repair

Further research is needed to fully understand the mechanisms by which GFAP and Vimentin influence axonal growth and plasticity in the injured CNS, to improve therapeutic strategies.

Study Limitations

1
The study was conducted on mice, and results may not directly translate to humans.
2
The mixed genetic background of the mice may introduce variability in the results.
3
The study focused on hemisection injuries, and the findings may not be applicable to other types of spinal cord injuries.

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