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Convective forces contribute to postā€traumatic degeneration after spinal cord injury

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Abstract
Spinal cord injury (SCI) initiates a complex cascade of chemical and biophysical phenomena that result in tissue swelling, progressive neural degeneration, and formation of a fluid-filled cavity. Previous studies show fluid pressure above the spinal cord (supraspinal) is elevated for at least 3ā€‰days after injury and contributes to a phase of damage called secondary injury. Currently, it is unknown how fluid forces within the spinal cord itself (interstitial) are affected by SCI and if they contribute to secondary injury. We find spinal interstitial pressure increases from āˆ’3ā€‰mmHg in the naive cord to a peak of 13ā€‰mmHg at 3ā€‰days post-injury (DPI) but relatively normalizes to 2ā€‰mmHg by 7ā€‰DPI. A computational fluid dynamics model predicts interstitial flow velocities up to 0.9ā€‰Ī¼m/s at 3ā€‰DPI, returning to near baseline by 7ā€‰DPI. By quantifying vascular leakage of Evans Blue dye after a cervical hemi-contusion in rats, we confirm an increase in dye infiltration at 3ā€‰DPI compared to 7ā€‰DPI, suggestive of higher fluid velocities at the time of peak fluid pressure. In vivo expression of the apoptosis marker caspase-3 is strongly correlated with regions of interstitial flow at 3ā€‰DPI, and exogenously enhancing interstitial flow exacerbates tissue damage. In vitro, we show overnight exposure of neuronal cells to low pathological shear stress (0.1ā€‰dynes/cm2) significantly reduces cell count and neurite length. Collectively, these results indicate that interstitial fluid flow and shear stress may play a detrimental role in post-traumatic neural degeneration.
Type
Article
Date
2025-01-14
Publisher
Wiley
Degree
Advisors
License
Attribution 4.0 International
License
http://creativecommons.org/licenses/by/4.0/