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Updated: Jun 26, 2026
Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging
Published on: April 6, 2014
Spreading depression expands traumatic injury in neocortical brain slices
Alanna J Church1, R David Andrew
1Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada.
Abstract:
Traumatic brain injury (TBI) is particularly common in young people, generating healthcare costs that can span decades. The cellular processes activated in the first minutes following injury are poorly understood, and the 3-4 h following trauma are crucial for reducing subsequent injury. Spreading depression (SD) is a profound inactivation of neurons and glia lasting 1-2 min that arises focally and migrates outward across gray matter. In the hours following focal stroke, the metabolic stress of energy reduction and recurring SD-like events (peri-infarct depolarizations, PIDs) interact to promote neuronal injury. Similar recurring depolarizations might evolve immediately following TBI and exacerbate neuronal damage peripheral to the impact site. To test this possibility and examine if certain drugs might limit damage by inhibiting what we term traumatic spreading depression (tSD), we developed a technique whereby a small weight was dropped onto a live slice of rat neocortex while imaging changes in light transmittance (LT). Imaging revealed a propagating front of increased LT arising at the border of the impact site. Traumatic SD significantly expanded the region of ensuing damage. Both tSD and subsequent damage were blocked by the NMDA receptor antagonist MK-801 (100 microM) or the sigma-1 receptor (sigma1R) ligands dextromethorphan (30 microM) or BD-1063 (100 microM). Co-application of the sigma1R antagonist (+)3-PPP with DM reversed the block as did lowering temperature from 35 degrees C to 32 degrees C. This study provides evidence that an event similar to peri-infarct depolarization can arise from an injury site in neocortex within seconds following impact and act to expand the region of acute neuronal damage.
Insights
Traumatic brain injury (TBI) triggers spreading depression (tSD) events that worsen brain damage. MK-801 and sigma-1 receptor ligands like dextromethorphan effectively block tSD and reduce injury.
Area of Science:
- Neuroscience
- Trauma Research
- Cellular Biology
Background:
- Traumatic brain injury (TBI) is a significant concern, especially in young individuals, leading to long-term healthcare costs.
- Early cellular events post-TBI are poorly understood, yet the initial hours are critical for mitigating secondary injury.
- Spreading depression (SD) is a known phenomenon of neuronal and glial inactivation that occurs after focal stroke and exacerbates damage.
Purpose of the Study:
- To investigate the occurrence of SD-like events immediately following TBI in neocortex.
- To determine if these traumatic spreading depression (tSD) events contribute to neuronal damage.
- To test the efficacy of specific drugs in inhibiting tSD and limiting TBI-induced damage.
Main Methods:
- Development of a novel technique involving dropping a small weight onto live rat neocortical slices.
- Imaging of light transmittance (LT) changes to detect propagating wave-like events.
- Pharmacological inhibition of NMDA receptors and sigma-1 receptors (sigma1R) to assess their role in tSD and damage.
Main Results:
- A propagating wave of increased LT, indicative of tSD, was observed originating from the TBI impact site.
- tSD was found to significantly expand the area of subsequent neuronal damage.
- The NMDA receptor antagonist MK-801 and sigma-1 receptor ligands (dextromethorphan, BD-1063) effectively blocked both tSD and the associated damage.
Conclusions:
- An SD-like event, termed traumatic spreading depression (tSD), can occur within seconds of neocortical impact.
- tSD plays a role in expanding acute neuronal damage following TBI.
- Inhibiting tSD with NMDA receptor antagonists or sigma-1 receptor ligands presents a potential therapeutic strategy for TBI.
