Manipulating microglia to promote axon regeneration
Funded in: 2021, 2022, 2023
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Problem: The inhibitory environment is an important hurdle for axon regeneration
Target: Develop strategies to create a permissive environment for axonal regrowth
Goal: Identify molecules and develop a microglia-based strategy to promote efficient wound healing
After spinal cord injury (SCI), an important hurdle for axon regeneration is the inhibitory environment, with massive accumulation of cells and extracellular matrix molecules (ECMs). Thus, it is important to develop strategies to create a permissive environment for axonal regrowth.
Neuroinflammation occurred at the lesion sites might be a potential target of such manipulation. At early post-injury stages, neuroinflammation is protective, but at later stages it accelerates scar formation and hinders regeneration. One of the key cell types that orchestrate both helpful and harmful neuroinflammatory responses is microglia, so microglia likely hold the key to the switch between states.
Recent studies from the neuroscientists suggested that neonatal microglia are able to organize efficient wound healing, creating a permissive environment for axon growth after neonatal SCI (Li et al., 2020), which provides new insights into manipulating wound healing in the adult SCI. Thus, the objective of this proposed study is to identify involved molecules and develop a microglia-based strategy to promote efficient wound healing, reduce scar formation in the lesion, thus supporting axon regeneration and function recovery in experimental SCI models.