David Stirling, University of Louisville, KSCIRC/ Neurological Surgery, Louisville, USA

Periaxonal swelling causes secondary white matter injury

Funded in: 2022, 2023, 2024

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Problem: Secondary degeneration
Target: Determine when and where periaxonal swelling occurs
Goal: Discovery of new neuroprotective treatments

Trauma to the spinal cord (SCI) often results in additional damage to the spinal cord wiring that allows us to sense and move within our environment. This additional damage is known as secondary degeneration. Neuroprotective treatments aim to block secondary degeneration to improve functional outcome after SCI. Importantly, this additional damage is delayed providing an opportunity to intervene to protect the wiring. However, how the wiring degenerates after SCI is poorly understood. Analogous to the electrical wires that power our home, the spinal cord wiring consists of axons and their support cells that produce myelin that protects and insulates axons. Together axons and myelin allow the rapid transmission of information and loss of these structures results in paralysis.

The researchers are investigating how myelin separates from axons after injury creating a space referred to as periaxonal swelling that they hypothesize prevents the wiring from working properly. This loss of contact of myelin would prevent communication between these structures important for their survival. Furthermore, the swelling creates a now accessible gap that allows toxic molecules to contact the axon that could cause additional degeneration and loss of function. 

The neuroscientists use an implantable spinal cord window that allows us to observe dynamic changes in both axons and myelin in real-time over the course of experimental contusive SCI that mimics human SCI. They expect to determine when and where periaxonal swelling occurs after SCI and what causes periaxonal swelling in the hopes that preventing it will protect the wiring of the spinal cord. They will test the effectiveness of potential blockers of periaxonal swelling to improve functional outcome by using behavioural testing after SCI. The information obtained may lead to the discovery of new neuroprotective treatments that can be applied in the clinic to improve outcome after SCI.