Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium
Name
nihms-1514423.pdf
Description
Accepted version
Size
1.99 MB
Format
Adobe PDF
Checksum (MD5)
72d929c2c97ec0060ce11fee4172d282
Author(s)
Ho, William W.
Grodzinsky, Alan J.
Date Issued
January 7, 2019
Journal
Nature biomedical engineering
Publisher
Springer Science and Business Media LLC
Citation
Seano, Giorgio et al. “Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium.” Nature biomedical engineering 3 (2019): 230-245 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
The compression of brain tissue by a tumour mass is believed to be a major cause of the clinical symptoms seen in patients with brain cancer. However, the biological consequences of these physical stresses on brain tissue are unknown. Here, via imaging studies in patients and by using mouse models of human brain tumours, we show that a subgroup of primary and metastatic brain tumours, classified as nodular on the basis of their growth pattern, exert solid stress on the surrounding brain tissue, causing a decrease in local vascular perfusion as well as neuronal death and impaired function. We demonstrate a causal link between solid stress and neurological dysfunction by applying and removing cerebral compression, which respectively mimic the mechanics of tumour growth and of surgical resection. We also show that, in mice, treatment with lithium reduces solid-stress-induced neuronal death and improves motor coordination. Our findings indicate that brain-tumour-generated solid stress impairs neurological function in patients, and that lithium as a therapeutic intervention could counter these effects.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Center for Biomedical Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41551-018-0334-7
