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Convective forces contribute to postātraumatic degeneration after spinal cord injury
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 3ādays 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 ā3āmmHg in the naive cord to a peak of 13āmmHg at 3ādays post-injury (DPI) but relatively normalizes to 2āmmHg by 7āDPI. A computational fluid dynamics model predicts interstitial flow velocities up to 0.9āĪ¼m/s at 3āDPI, returning to near baseline by 7āDPI. By quantifying vascular leakage of Evans Blue dye after a cervical hemi-contusion in rats, we confirm an increase in dye infiltration at 3āDPI compared to 7āDPI, 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 3āDPI, and exogenously enhancing interstitial flow exacerbates tissue damage. In vitro, we show overnight exposure of neuronal cells to low pathological shear stress (0.1ādynes/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/