Andrew Stewart, University of Kentucky, Physiology, SCoBIRC, Lexington, USA

Improving axon regeneration through delayed macrophage manipulation

Funded in: 2022, 2023, 2024

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Problem: Chronic inflammation is inhibitory to regeneration 
Target: Macrophages that limit repair and regeneration
Goal: Improve regeneration in chronic SCI

Chronic spinal cord injury (SCI) is hallmarked by persistent functional deficits and an emergence of molecules that inhibit growth and regeneration. These growth inhibitors are maintained permanently in chronic SCI and are considered barriers to treatment strategies aimed at restoring function through nervous system regeneration and plasticity.

Many inhibitory molecules that arise after SCI emerge due to inflammation occurring in the acutely injured environment. Macrophages are an immune cell that enter into acutely injured spinal cords, orchestrate the production of growth inhibitors, and persist in the lesion permanently. This project seeks to determine if macrophages persisting within chronic lesions limit repair and regeneration.

The researchers will be utilizing methods to deplete macrophages from chronically injured spinal cords to determine if their continued presence is causal to a sustained growth inhibitory environment. Next, the neuroscientists will determine if depleting macrophages can improve regenerative treatment approaches in chronic SCI. Finally, they aim to better understand the chronic SCI environment by constructing a single-cell RNA sequencing database to determine what role macrophages are exhibiting in chronic SCI. The single-cell RNA sequencing database will provide a tool for the SCI research field that can lead to more hypotheses and treatment approaches generated for the chronic SCI condition.

The neuroscientists expect their work to determine if chronic inflammation is inhibitory to axon regeneration and regenerative therapies in the chronic SCI environment. Further, they expect to develop and test more effective regenerative strategies applicable to chronic SCI.