Title

Solid Stress in Brain Tumours Causes Neuronal Loss and Neurological Dysfunction and Can Be Reversed by Lithium

Publication Date

1-7-2019

Journal

Nature Biomedical Engineering

Volume

https://doi.org/10.1038/s41551-018-0334-7

First Page

1

Last Page

16

Department

Biomedical Engineering

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.

DOI

https://doi.org/10.1038/s41551-018-0334-7

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