Issue 23, 2022

Axons-on-a-chip for mimicking non-disruptive diffuse axonal injury underlying traumatic brain injury

Abstract

Diffuse axonal injury (DAI) is the most severe pathological feature of traumatic brain injury (TBI). However, how primary axonal injury is induced by transient mechanical impacts remains unknown, mainly due to the low temporal and spatial resolution of medical imaging approaches. Here we established an axon-on-a-chip (AoC) model for mimicking DAI and monitoring instant cellular responses. Integrating computational fluid dynamics and microfluidic techniques, DAI was induced by injecting a precisely controlled micro-flux in the transverse direction. The clear correlation between the flow speed of injecting flux and the severity of DAI was elucidated. We next used the AoC to investigate the instant intracellular responses underlying DAI and found that the dynamic formation of focal axonal swellings (FAS) accompanied by Ca2+ surge occurs during the flux. Surprisingly, periodic axonal cytoskeleton disruption also occurs rapidly after the flux. These instant injury responses are spatially restricted to the fluxed axon, not affecting the overall viability of the neuron in the acute stage. Compatible with high-resolution live microscopy, the AoC provides a versatile system to identify early mechanisms underlying DAI, offering a platform for screening effective treatments to alleviate TBI.

Graphical abstract: Axons-on-a-chip for mimicking non-disruptive diffuse axonal injury underlying traumatic brain injury

Supplementary files

Article information

Article type
Paper
Submitted
05 Aug 2022
Accepted
20 Oct 2022
First published
24 Oct 2022

Lab Chip, 2022,22, 4541-4555

Axons-on-a-chip for mimicking non-disruptive diffuse axonal injury underlying traumatic brain injury

X. Pan, J. Li, W. Li, H. Wang, N. Durisic, Z. Li, Y. Feng, Y. Liu, C. Zhao and T. Wang, Lab Chip, 2022, 22, 4541 DOI: 10.1039/D2LC00730D

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