Recovery of Retinal Terminal Fields after Traumatic Brain Injury: Evidence of Collateral Sprouting and Sexual
Athanasios S Alexandris1, Jaeyoon Yi1, Chang Liu1
1Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Summary
Surviving axons sprout to repair brain circuits after traumatic brain injury (TBI). This collateral sprouting restores visual function, though recovery shows sex differences and some independence from Wallerian degeneration.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Traumatic Brain Injury Research
Background:
- The central nervous system has limited regenerative capacity, but functional recovery after injury occurs.
- Traumatic brain injury (TBI) disrupts neural connectivity, and repair mechanisms are poorly understood.
- Retinal ganglion cell (RGC) axon and synapse repair after TBI remains an area needing further investigation.
Purpose of the Study:
- To investigate the structural and functional changes in visual pathways after diffuse traumatic axonal injury (TAI) in a mouse model.
- To explore the role of collateral sprouting in repairing TAI-induced connectivity disruptions.
- To assess functional recovery of visual pathways and identify potential sex differences in the repair process.
Main Methods:
- Utilized an Impact-acceleration TBI mouse model to induce diffuse traumatic axonal injury.
- Genetically labeled RGC axons and synapses using AAV transduction.
- Employed anterograde and transsynaptic tracers, c-Fos expression, and pattern-reversal visual evoked potentials (pVEPs) to assess connectivity and function.
Main Results:
- TAI caused ~50% loss of RGC axons, but surviving axons underwent collateral sprouting, restoring terminal density.
- Transsynaptic tracing and c-Fos mapping confirmed reestablished neural connectivity.
- Significant visual function recovery was observed via pVEPs, with notable sexual dimorphism (females showed delayed/incomplete repair).
- Collateral sprouting occurred normally in Sarm1 knockout mice, suggesting partial independence from Wallerian degeneration.
Conclusions:
- Collateral sprouting is a key mechanism for repairing neural circuits after TAI in the visual system.
- Restoration of structural and functional connectivity contributes to visual recovery post-TBI.
- The findings highlight potential therapeutic targets for TBI by leveraging homotypic collateral sprouting, while noting sex-based differences in recovery.
Keywords:
collateral sproutingdiffuse axonal injuryreactive synaptogenesisregenerationsex differences
