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Macrophages and Microglia Produce Local Trophic Gradients That Stimulate Axonal Sprouting Toward but Not beyond the
P E Batchelor1, M J Porritt, P Martinello
1Departments of Medicine, Neurology, The University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia.
Molecular and Cellular Neurosciences
|December 25, 2002
Summary
Axons in the injured central nervous system (CNS) grow towards wound edges, guided by activated microglia and macrophages. However, growth stops at the wound margin due to a decrease in crucial neurotrophic factors within the lesion core.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Axonal sprouting occurs after central nervous system (CNS) injury, but regeneration across the lesion site is typically unsuccessful.
- Understanding the cellular and molecular interactions at the injury site is crucial for promoting CNS repair.
Purpose of the Study:
- To investigate the relationship between sprouting axons and reactive glial cells (microglia) and macrophages following CNS injury.
- To elucidate the role of neurotrophic factors in guiding axonal growth towards and away from the wound site.
Main Methods:
- Utilized a dopaminergic sprouting model in the injured striatum.
- Examined the interactions between sprouting fibers, microglia, and macrophages using histological analysis.
- Assessed the expression of Brain-Derived Neurotrophic Factor (BDNF) and Glial cell line-Derived Neurotrophic Factor (GDNF) in relation to cell types and proximity to the wound.
Main Results:
- Sprouting axons formed close associations with activated microglia near the wound edge and complex plexuses around macrophages at the margin.
- Axonal growth ceased at the wound edge despite the presence of macrophages, and failed to enter the wound core.
- BDNF expression by microglia increased towards the wound edge, while GDNF expression by macrophages peaked at the margin. Both factors were reduced in the wound interior.
Conclusions:
- Axonal growth is directed towards the wound margin by an increasing trophic gradient from activated microglia and macrophages.
- Maximal neurotrophic factor expression at the wound edge, coupled with a poor trophic environment within the wound core, inhibits further axonal regeneration.