Exercise-induces changes in cerebral blood flow: an in vitro and in vivo investigation of vascular responses

Weaver, Samuel Roger Clayton ORCID: 0000-0002-6585-1995 (2022). Exercise-induces changes in cerebral blood flow: an in vitro and in vivo investigation of vascular responses. University of Birmingham. Ph.D.

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Abstract

Greater physical fitness is linked to improved cerebrovascular health and brain function. However, acute responses to exercise can differ depending on exercise intensity, as well as by the specific exercise protocol used. While the endothelium plays an essential role in driving responses to stimuli and adaptation in the vasculature, the cellular responses to transient changes in circulating environment are poorly understood. This thesis investigated the effect of different exercise protocols on the responses seen in the cerebrovasculature and circulating environment in vivo, alongside the use of endothelial cell culture models to examine cellular responses to ex vivo application of plasma and serum samples taken from exercising participants.

Cerebral haemodynamic responses were largely comparable between moderate intensity continuous exercise and clinical guideline-based high intensity interval exercise protocols. In contrast, sprint-interval exercise induced a unique pattern in middle cerebral artery velocity, whereby velocity was suppressed during the interval effort but then “rebounded” during recovery. A novel, semi-automated analysis methodology was developed to explore this temporal pattern further, showing that while intensity does modulate rebound characteristics the factors influencing temporal patterns in cerebral blood flow are likely multi-faceted. Finally, significant, intensity-dependent changes in VEGF, BDNF, IGF-1 and lactate were seen in response to exercise. However, ex vivo treatment of endothelial cells with samples taken pre- and post-exercise did not reveal any significant impact on cellular function, although further research is needed to fully illuminate the role of the circulating microenvironment in altering acute endothelial function.

Collectively, these findings highlight that the choice of exercise protocol can have a profound impact on cerebrovascular haemodynamics and responses in the circulating microenvironment. While the contribution of these two domains to long-term adaptive benefits to cerebrovascular health remains to be determined, it may be that the optimal exercise bout to elicit both haemodynamic- and neurotropic-induced adaptive changes may be a hybrid of the protocols tested here. Finally, future research should embrace the exciting opportunities and challenges that the application of translational research presents, to continue exploring the impact that exercise has on the brain from a cellular and systemic perspective.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):