Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium

Giorgio Seano, Hadi T. Nia, Kyrre E. Emblem, Meenal Datta, Jun Ren, Shanmugarajan Krishnan, Jonas Kloepper, Marco Da Cunha Pinho, William W. Ho, Mitrajit Ghosh, Vasileios Askoxylakis, Gino B. Ferraro, Lars Riedemann, Elizabeth R. Gerstner, Tracy T. Batchelor, Patrick Y. Wen, Nancy U. Lin, Alan J. Grodzinsky, Dai Fukumura, Peigen HuangJames W. Baish, Timothy P. Padera, Lance L. Munn, Rakesh K. Jain

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
JournalNature Biomedical Engineering
DOIs
StateAccepted/In press - Jan 1 2019

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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    Seano, G., Nia, H. T., Emblem, K. E., Datta, M., Ren, J., Krishnan, S., Kloepper, J., Da Cunha Pinho, M., Ho, W. W., Ghosh, M., Askoxylakis, V., Ferraro, G. B., Riedemann, L., Gerstner, E. R., Batchelor, T. T., Wen, P. Y., Lin, N. U., Grodzinsky, A. J., Fukumura, D., ... Jain, R. K. (Accepted/In press). Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-018-0334-7