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Altered cerebral blood flow and cerebrovascular function after voluntary exercise in adult mice

Brain Structure and Function volume 222, pages 3395–3405 (2017)Cite this article

Abstract

The beneficial effects of physical exercise on brain health are well documented, yet how exercise modulates cerebrovascular function is not well understood. This study used continuous arterial spin labeling magnetic resonance imaging with a hypercapnic challenge to examine changes in cerebral blood flow and vascular function after voluntary exercise in healthy, adult mice. Thirty exercise mice and twenty-one control mice were imaged prior to the start of the exercise regime (at 12 weeks of age) and after 4 weeks of voluntary exercise. After the second in vivo imaging session, we performed high-resolution ex vivo anatomical brain imaging to correlate the structural brain changes with functional measures of flow and vascular reserve. We found that exercise resulted in increases in the normocapnic and hypercapnic blood flow in the hippocampus. Moreover, the change in normocapnic blood flow between pre-exercise and post-exercise was positively correlated to the hippocampal structure volume following exercise. There was no overall effect of voluntary exercise on blood flow in the motor cortex. Surprisingly, the hypercapnic hippocampal blood flow when measured prior to the start of exercise was predictive of subsequent exercise activity. Moreover, exercise was found to normalize this pre-existing difference in hypercapnic blood flow between mice.

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Abbreviations

2PFM:

Two-photon fluorescence microscopy

CASL:

Continuous arterial spin labeling

CBF:

Cerebral blood flow

CVR:

Cerebrovascular reactivity

FDR:

False discovery rate

FOV:

Field-of-view

PBS:

Phosphate-buffered saline

PFA:

Paraformaldehyde

ROI:

Region-of-interest

tcpCO2 :

Transcutaneous carbon dioxide

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Affiliations

  1. Mouse Imaging Centre, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 2H7, Canada

    Lindsay S. Cahill, Jonathan Bishop, Lisa M. Gazdzinski & John G. Sled

  2. Sunnybrook Research Institute, Toronto, ON, Canada

    Adrienne Dorr & Bojana Stefanovic

  3. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Bojana Stefanovic & John G. Sled

Authors
  1. Lindsay S. Cahill
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  2. Jonathan Bishop
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  3. Lisa M. Gazdzinski
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  4. Adrienne Dorr
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  5. Bojana Stefanovic
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  6. John G. Sled
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Corresponding author

Correspondence to Lindsay S. Cahill.

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Funding

This work was supported by the Canadian Institutes of Health Research Grant MOP231389.

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Supplementary material 1 (DOCX 49 KB)

429_2017_1409_MOESM2_ESM.png

Online Resource 1. Coronal ex vivo MR slices showing the difference in relative structure volume between the exercise (n = 25) and control (n = 19) groups. The volumes of the hippocampus and the occipital lobe of the cerebral cortex were found to be significantly larger post-exercise (10% FDR). The percentage change in brain structure volume is indicated by the color bar on the left (PNG 953 KB)

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Cahill, L.S., Bishop, J., Gazdzinski, L.M. et al. Altered cerebral blood flow and cerebrovascular function after voluntary exercise in adult mice. Brain Struct Funct 222, 3395–3405 (2017). https://doi.org/10.1007/s00429-017-1409-z

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  • DOI: https://doi.org/10.1007/s00429-017-1409-z

Keywords

  • Cerebral blood flow
  • Cerebrovascular function
  • Hippocampus
  • Mouse MRI
  • Voluntary exercise