Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation

Gretchen Wolff, Sarah J. Davidson, Jagoda K. Wrobel, Michal J Toborek

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

Original languageEnglish (US)
Pages (from-to)811-817
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume463
Issue number4
DOIs
StatePublished - Apr 11 2015

Fingerprint

Blood-Brain Barrier
Tumors
Brain
Neoplasm Metastasis
Cells
Neoplasms
Microvessels
Running
Wheels
Occludin
Tight Junction Proteins
Lewis Lung Carcinoma
Tight Junctions
Internal Carotid Artery
Surgery
Oxidation
Proteins

Keywords

  • Bioluminescence
  • Blood-brain barrier
  • Exercise
  • Metastasis
  • Tight junction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation. / Wolff, Gretchen; Davidson, Sarah J.; Wrobel, Jagoda K.; Toborek, Michal J.

In: Biochemical and Biophysical Research Communications, Vol. 463, No. 4, 11.04.2015, p. 811-817.

Research output: Contribution to journalArticle

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