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

11 Citations (Scopus)

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

Fingerprint

Lithium
Brain Neoplasms
Tumors
Brain
Tissue
Growth
Mechanics
Blood Vessels
Neoplasms
Perfusion
Therapeutics
Compaction
Imaging techniques

ASJC Scopus subject areas

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

Cite this

Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. / Seano, Giorgio; Nia, Hadi T.; Emblem, Kyrre E.; Datta, Meenal; Ren, Jun; Krishnan, Shanmugarajan; Kloepper, Jonas; Da Cunha Pinho, Marco; Ho, William W.; Ghosh, Mitrajit; Askoxylakis, Vasileios; Ferraro, Gino B.; Riedemann, Lars; Gerstner, Elizabeth R.; Batchelor, Tracy T.; Wen, Patrick Y.; Lin, Nancy U.; Grodzinsky, Alan J.; Fukumura, Dai; Huang, Peigen; Baish, James W.; Padera, Timothy P.; Munn, Lance L.; Jain, Rakesh K.

In: Nature Biomedical Engineering, 01.01.2019.

Research output: Contribution to journalArticle

Seano, G, Nia, HT, Emblem, KE, Datta, M, Ren, J, Krishnan, S, Kloepper, J, Da Cunha Pinho, M, Ho, WW, Ghosh, M, Askoxylakis, V, Ferraro, GB, Riedemann, L, Gerstner, ER, Batchelor, TT, Wen, PY, Lin, NU, Grodzinsky, AJ, Fukumura, D, Huang, P, Baish, JW, Padera, TP, Munn, LL & Jain, RK 2019, '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
Seano, Giorgio ; Nia, Hadi T. ; Emblem, Kyrre E. ; Datta, Meenal ; Ren, Jun ; Krishnan, Shanmugarajan ; Kloepper, Jonas ; Da Cunha Pinho, Marco ; Ho, William W. ; Ghosh, Mitrajit ; Askoxylakis, Vasileios ; Ferraro, Gino B. ; Riedemann, Lars ; Gerstner, Elizabeth R. ; Batchelor, Tracy T. ; Wen, Patrick Y. ; Lin, Nancy U. ; Grodzinsky, Alan J. ; Fukumura, Dai ; Huang, Peigen ; Baish, James W. ; Padera, Timothy P. ; Munn, Lance L. ; Jain, Rakesh K. / Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. In: Nature Biomedical Engineering. 2019.
@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 {Da Cunha Pinho}, Marco 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.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41551-018-0334-7",
language = "English (US)",
journal = "Nature Biomedical Engineering",
issn = "2157-846X",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium

AU - Seano, Giorgio

AU - Nia, Hadi T.

AU - Emblem, Kyrre E.

AU - Datta, Meenal

AU - Ren, Jun

AU - Krishnan, Shanmugarajan

AU - Kloepper, Jonas

AU - Da Cunha Pinho, Marco

AU - Ho, William W.

AU - Ghosh, Mitrajit

AU - Askoxylakis, Vasileios

AU - Ferraro, Gino B.

AU - Riedemann, Lars

AU - Gerstner, Elizabeth R.

AU - Batchelor, Tracy T.

AU - Wen, Patrick Y.

AU - Lin, Nancy U.

AU - Grodzinsky, Alan J.

AU - Fukumura, Dai

AU - Huang, Peigen

AU - Baish, James W.

AU - Padera, Timothy P.

AU - Munn, Lance L.

AU - Jain, Rakesh K.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85059679725&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059679725&partnerID=8YFLogxK

U2 - 10.1038/s41551-018-0334-7

DO - 10.1038/s41551-018-0334-7

M3 - Article

C2 - 30948807

AN - SCOPUS:85059679725

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

SN - 2157-846X

ER -