@article{bcc7750527084419b8dd04e829eac3b6,
title = "Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium",
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.",
author = "Giorgio Seano and Nia, {Hadi T.} and Emblem, {Kyrre E.} and Meenal Datta and Jun Ren and Shanmugarajan Krishnan and Jonas Kloepper and Pinho, {Marco C.} and Ho, {William W.} and Mitrajit Ghosh and Vasileios Askoxylakis and Ferraro, {Gino B.} and Lars Riedemann and Gerstner, {Elizabeth R.} and Batchelor, {Tracy T.} and Wen, {Patrick Y.} and Lin, {Nancy U.} and Grodzinsky, {Alan J.} and Dai Fukumura and Peigen Huang and Baish, {James W.} and Padera, {Timothy P.} and Munn, {Lance L.} and Jain, {Rakesh K.}",
note = "Funding Information: We thank A. Ivinson (UK Dementia Research Institute), M. A. Moskowitz and M. J. Whalen (MGH) for critical discussion and insightful suggestions; S. Roberge, M. Duquette, C. Smith and E. L. Jones (MGH) for technical support, H. Wakimoto (MGH) for the MGG8 cell line and O. Rapalino (MGH) for help with the pre-operative clinical study. This work was supported by the National Cancer Institute (NCI; P01-CA080124, P50-CA165962, R01-CA129371, R01-CA208205, U01-CA 224348), NCI Outstanding Investigator Award (R35-CA197743), the Lustgarten Foundation, the Ludwig Center at Harvard, the National Foundation for Cancer Research and the Gates Foundation (R.K.J), R01-HL128168 (to J.W.B., T.P.P. and L.L.M.), DP2OD008780 (T.P.P.), R01CA214913 (T.P.P.), P41EB015903 (Center for Biomedical OCT Research and Translation), NIH/NINDS P30NS045776 (EM facility core) and P30-CA14051 from NCI (Koch Institute Genomics core). This work was also supported in part by the Susan G. Komen Foundation Fellowship PDF14301739, Fondation ARC pour la recherche sur le cancer and the INSERM-CNRS ATIP-Avenir grant (G.S.), NCI F32-CA216944-01 (H.T.N.), the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 (grant agreement no. 758657), the South-Eastern Norway Regional Health Authority grants 2017073, 2016102 and 2013069, the Research Council of Norway grants 261984 and ES435705, the Norwegian Cancer Society grants 6817564 and 3434180 (K.E.E.), F31HL126449 from the National Heart, Lung, and Blood Institute at the NIH (M.D.), SolidarImmun fellowship (J.K.), Feodor-Lynen Postdoctoral Fellowship from Alexander von Humboldt Foundation (M.G.) and Deutsche Forschungsgemeinschaft AS422-2/1 (V.A.). Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2019",
month = mar,
day = "1",
doi = "10.1038/s41551-018-0334-7",
language = "English (US)",
volume = "3",
pages = "230--245",
journal = "Nature Biomedical Engineering",
issn = "2157-846X",
publisher = "Nature Publishing Group",
number = "3",
}