Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretch in vitro

Frontiers in Cellular Neuroscience, 2023 · DOI: 10.3389/fncel.2023.1111403 · Published: March 29, 2023

Simple Explanation

This study investigates how dorsal root ganglion neurons (DRGN) respond to mechanical stretch, similar to what happens in traumatic brain injury (TBI). The researchers compared DRGN's response to that of cortical neurons, which are commonly used in TBI research. They found that DRGN axons show similar early responses to stretch injury as cortical neurons, including the formation of undulations, elongation, recovery, and degeneration. Both types of axons also experienced comparable calcium influx. These findings suggest DRGNs could be a useful model for studying TBI, especially for understanding injury progression in myelinated and adult neurons, which are limitations of using cortical neurons.

Study Duration

Not specified

Participants

E17 Sprague-Dawley rat pups

Evidence Level

In vitro study

Key Findings

1
DRGN and cortical axons exhibit similar morphological changes, including undulation formation, elongation, and recovery, in response to severe stretch injury.
2
Both DRGN and cortical axons experience comparable degrees of calcium influx after stretch injury, which can be prevented by blocking sodium channels with lidocaine (in DRGNs) or tetrodotoxin (in cortical neurons).
3
Stretch injury causes calcium-activated proteolysis of sodium channels in DRGN axons, similar to cortical axons, and this proteolysis can be prevented by lidocaine or protease inhibitors.

Research Summary

The study investigates the response of dorsal root ganglion neurons (DRGN) to mechanical stretch injury, comparing them to cortical neurons, in an in vitro model of traumatic brain injury (TBI). Results show that DRGN axons share similar early responses to stretch injury as cortical neurons, including morphological changes, calcium influx, and sodium channel proteolysis, suggesting DRGNs could be a viable model for studying TBI mechanisms. The utility of DRGNs lies in their ability to be myelinated and cultured from adult sources, addressing limitations of cortical cultures and allowing for future studies of TBI injury progression in myelinated and adult neurons.

Practical Implications

New Model for TBI Research

DRGNs can serve as a viable in vitro model to study the cellular events initiated by mechanical stretch and the associated secondary injury mechanisms in TBI.

Study of Myelinated Axons

DRGNs can be myelinated in vitro, enabling the study of DAI, a pathology primarily occurring in white matter tracts, which is not feasible with cortical cultures.

Adult Neuron Studies

DRGNs can be isolated and cultured from adult animals and humans, addressing a major criticism of the clinical relevance of in vitro TBI models that primarily use embryonic neurons.

Study Limitations

1
DRGNs have distinct differences from brain-derived neurons including voltage gated ion channel expression, signaling receptors, and electrophysiological activity
2
Cortical cultures are not myelinated whereas DAI is a pathology that occurs primarily in white matter tracts.
3
There are well-known differences in the response of embryonic and adult neurons to injury and has been a major criticism of the clinical relevance of in vitro TBI models

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