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

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 hours) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 hours 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 hours 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.

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women

“…Activation of rho GTPases is related to the decrease in the expression of proteins from tight junction (such as claudin-5), and increase in BBB permeability through monocyte migration (Persidsky et al 2006). Evidence has demonstrated that exercising mice had less activation of rho kinase than sedentary animals, supporting the idea that exercise practice could maintain the BBB integrity through these mechanisms (Wolff et al 2015).…”

Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

“…Male C57BL/6 J mice (Jackson Laboratories) were allowed to acclimatize to the animal facility for one week with free access to food and water. They were then infused with EcoHIV/NDK (200 ng of p24) into the internal carotid artery using a method previously described589293. Control animals received saline.…”

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

“…Additionally, physical activity promoted Aβ clearance from brain to blood via upregulation of LRP1 [241,242] and downregulation of RAGE [91] at the BBB. Mice without access to a running wheel had decreased occludin tight junction levels and disrupted BBB integrity [243]. Although recent attention has been given to exercise, additional studies are needed to more completely understand the mechanism underlying its beneficial effects.…”