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Nat Biomed Eng. 2019 Mar;3(3):230-245. doi: 10.1038/s41551-018-0334-7. Epub 2019 Jan 7.

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

Author information

1
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
2
Institut Curie Research Center, PSL Research University, Inserm U1021, CNRS UMR3347, Orsay, France.
3
The Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
4
Department of Chemical and Biological Engineering, Tufts University, Medford, MA, USA.
5
Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA.
6
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
7
Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
8
Department of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA.
9
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
10
Center for Biomedical Engineering, Departments of Mechanical, Electrical and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
11
Department of Biomedical Engineering, Bucknell University, Lewisburg, PA, USA.
12
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. jain@steele.mgh.harvard.edu.

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.

Comment in

PMID:
30948807
PMCID:
PMC6452896
DOI:
10.1038/s41551-018-0334-7
[Indexed for MEDLINE]
Free PMC Article

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