Abstract
The brain’s extracellular matrix (ECM) is a dynamic protein-based scaffold within which neural networks can form, self-maintain, and re-model. When the brain incurs injuries, microscopic tissue tears and active ECM re-modelling give way to abnormal brain structure and function including the presence of ectopic cells. Post-mortem and neuroimaging data suggest that the brains of jet pilots and astronauts, who are exposed to rotational forces, accelerations, and microgravity, display brain anomalies which could be indicative of a mechanodisruptive pathology. Here we present a model of non-impact-based brain injury induced by matrix deformation following mechanical shaking. Using a bioengineered 3D neural tissue platform, we designed a repetitive shaking paradigm to simulate subtle rotational acceleration. Our results indicate shaking induced ectopic cell clustering that could be inhibited by physically restraining tissue movement. Imaging revealed that the collagen substrate surrounding cells was deformed following shaking. Applied to neonatal rat brains, shaking induced deformation of extracellular spaces within the cerebral cortices and reduced the number of cell bodies at higher accelerations. We hypothesize that ECM deformation may represent a more significant role in brain injury progression than previously assumed and that the present model system contributes to its understanding as a phenomenon.
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Abbreviations
- ECM:
-
Extracellular matrix
- rpm:
-
Revolutions per minute
- DAPI:
-
4′,6-Diamidino-2-phenylindole
- CA:
-
Calcein-AM
- PI:
-
Propidium iodide
- WBV:
-
Whole-body vibrations
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Acknowledgments
The authors would like to thank Martin Hunter, Will Collins, and Disha Sood for their technical expertise and assistance. This work was supported by the NIH (R01NS092847, P41EB027062, Research Infrastructure Grant NIHS10 OD021624).
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Rouleau, N., Murugan, N.J., Rusk, W. et al. Matrix Deformation with Ectopic Cells Induced by Rotational Motion in Bioengineered Neural Tissues. Ann Biomed Eng 48, 2192–2203 (2020). https://doi.org/10.1007/s10439-020-02561-6
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DOI: https://doi.org/10.1007/s10439-020-02561-6