SCF + G‑CSF treatment in the chronic phase of severe TBI enhances axonal sprouting in the spinal cord and synaptic pruning in the hippocampus

Acta Neuropathologica Communications, 2021 · DOI: https://doi.org/10.1186/s40478-021-01160-3 · Published: May 21, 2021

Regenerative Medicine Neurology Brain Injury

Simple Explanation

Traumatic brain injury (TBI) is a significant cause of lasting disability in young adults, and effective treatments, particularly for the chronic phase, are lacking. This study investigates the potential of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF + G-CSF) treatment to aid recovery in a severe TBI mouse model. The research demonstrates that repeated SCF + G-CSF treatments, when started three months post-TBI, outperform single treatments. These repeated treatments encourage the growth of nerve fibers in the spinal cord, specifically the corticospinal tract, and help to restore balance in the hippocampus by promoting the removal of excess synapses through microglial synaptic pruning. These restorative changes are connected with enhancements in somatosensory-motor skills and spatial learning. Moreover, the treatment counters the degeneration of microglia, which is typically induced by severe TBI, in both the cortex and hippocampus. These results highlight the therapeutic capabilities and possible mechanisms of SCF + G-CSF treatment in repairing brain damage during the chronic phase of severe TBI.

Study Duration

25 weeks after the final treatment

Participants

40 male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
Repeated SCF + G-CSF treatments in the chronic phase of severe TBI lead to better neurological function improvement than single SCF + G-CSF treatment.
2
SCF + G-CSF treatment promotes corticospinal tract (CST) sprouting, ameliorates severe TBI-induced dendritic spine loss and microglial degeneration.
3
SCF + G-CSF treatment enhances removal of the severe TBI-induced overgrowth of synapses by microglial cell-mediated synaptic pruning.

Research Summary

This study investigates the neurorestorative efficacy of repeated SCF + G-CSF treatment in the chronic phase of severe TBI, demonstrating its superiority over single treatments. The treatment enhances contralesional corticospinal tract sprouting, ameliorates microglial degeneration, and promotes synaptic pruning in the hippocampus, leading to improved somatosensory-motor function and spatial learning. The findings reveal the therapeutic potential and possible mechanism of SCF + G-CSF treatment in brain repair during the chronic phase of severe TBI.

Practical Implications

Therapeutic Potential

SCF + G-CSF treatment shows promise as a therapeutic intervention for brain repair in the chronic phase of severe TBI.

Neurological Improvement

Repeated SCF + G-CSF treatments lead to better neurological function improvement compared to single treatments.

Synaptic Re-balancing

SCF + G-CSF treatment promotes synaptic re-balancing in the hippocampus by enhancing microglial function of synaptic pruning.

Study Limitations

1
The molecular mechanisms of SCF + G-CSF-enhanced contralateral corticospinal tract sprouting are not addressed.
2
The mechanisms of SCF + G-CSF-ameliorated microglial pathology in the chronic phase of severe TBI are not addressed.
3
The lack of a sham control group in the in vivo experiment assessing uptake of synapses by microglia (Fig. 8)

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