Negligible influence of moderate to severe hyperthermia on blood-brain barrier permeability and neuronal parenchymal integrity in healthy men
Shepley BR, Ainslie PN, Hoiland RL, Donnelly J, Sekhon MS, Zetterberg H, Blennow K, Bain AR
Journal of applied physiology (Bethesda, Md. : 1985) · 9 citations
How it was studied
- Design
- Controlled clinical trial (classified by our AI screen)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Alzheimer's Drug Discovery Foundation
- Government
- EU Joint Programme – Neurodegenerative Disease Research
- Government
- Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada
- Nonprofit
- Hjärnfonden
- Government
- Vetenskapsrådet
- Nonprofit
- Alzheimerfonden
- University or hospital
- UK Dementia Research Institute
- Government
- European Research Council
- Government
- H2020 European Research Council
- Government
- Swedish State Support for Clinical Research
- Government
- Medical Research Council
- Nonprofit
- Alzheimer's Drug Discovery Foundation
- Government
- EU Joint Programme - Neurodegenerative Disease Research
- Grants
- Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-05760); European Research Council (681712); Hjärnfonden (FO2017‑0243); Vetenskapsrådet (2017-00915); Alzheimer's Drug Discovery Foundation (201809–2016862); Alzheimerfonden (AF-742881); EU Joint Programme – Neurodegenerative Disease Research (JPND2019-466-236); H2020 European Research Council (681712); Vetenskapsrådet (2018-02532); Alzheimer's Drug Discovery Foundation (#RDAPB‐201809‐2016615)
Based on 13 listed funder(s).
Publication
- Published
- 2021-01-14 · J Appl Physiol (1985) · vol. 130 · issue 3 · pp. 792–800
- Publisher
- American Physiological Society
- Cited
- 12 citations · more than 68% of similar papers · 0.8× the field average
- References
- 64 works
- Access
- Open access (repository copy)
- Research areas
- Thermoregulation and physiological responses · Thermal Regulation in Medicine · Climate Change and Health Impacts
- Keywords
- Hyperthermia, Blood–brain barrier, Parenchyma, Medicine, Neurovascular bundle, Structural integrity, Heat stress, Evans Blue, Extravasation, Anesthesia, Pathology, Neuroscience, Internal medicine, Central nervous system, Psychology, Biology
- MeSH
- blood-brain barrier, humans, hyperthermia, induced, cerebrovascular circulation, permeability, male, hyperthermia
8 authors
From CA, GB, SE
- Brooke R. ShepleyUniversity of Windsor
- Philip Neil AinslieUniversity of British Columbia; University of British Columbia, Okanagan Campus
- Ryan L. HoilandUniversity of British Columbia; Vancouver General Hospital; University of British Columbia, Okanagan Campus
- Joseph E. DonnellyUniversity of Cambridge; Addenbrooke's Hospital
- Mypinder S. SekhonUniversity of British Columbia; University of British Columbia, Okanagan Campus
- Henrik ZetterbergSahlgrenska University Hospital; UK Dementia Research Institute; National Hospital for Neurology and Neurosurgery; UCL Queen Square Institute of Neurology; University College London; University of Gothenburg
Abstract
With growing use for hyperthermia as a cardiovascular therapeutic, there is surprisingly little information regarding the acute effects it may have on the integrity of the neurovascular unit (NVU). Indeed, relying on animal data would suggest hyperthermia comparable to levels attained in thermal therapy will disrupt the blood-brain barrier (BBB) and damage the cerebral parenchymal cells. We sought to address the hypothesis that controlled passive hyperthermia is not sufficient to damage the NVU in healthy humans. Young men (n = 11) underwent acute passive heating until +2°C or absolute esophageal temperature of 39.5°C. The presence of BBB opening was determined by trans-cerebral exchange kinetics (radial-arterial and jugular venous cannulation) of S100B. Neuronal parenchymal damage was determined by the trans-cerebral exchange of tau protein, neuron-specific enolase (NSE), and neurofilament-light protein (NF-L). Cerebral blood flow to calculate exchange kinetics was measured by duplex ultrasound of the right internal carotid and left vertebral artery. Passive heating was performed via a warm-water perfused suit. In hyperthermia, there was no increase in the cerebral exchange of S100B (P = 0.327), tau protein (P = 0.626), NF-L (P = 0.447), or NSE (P = 0.908) suggesting the +2°C core temperature is not sufficient to acutely stress the NVU in healthy men. However, there was a significant condition effect (P = 0.028) of NSE, corresponding to a significant increase in arterial (P = 0.023) but not venous (P = 0.173) concentrations in hyperthermia, potentially indicating extra-cerebral release of NSE. Collectively, results from the present study support the notion that in young men there is little concern for NVU damage with acute hyperthermia of +2 °C.NEW & NOTEWORTHY The acute effects of passive whole-body hyperthermia on the integrity of the neurovascular unit (NVU) in humans have remained unclear. We demonstrate that passive heating for ∼1 h until an increase of +2°C esophageal temperature in healthy men does not increase the cerebral release of neuronal parenchymal stress biomarkers, suggesting the NVU integrity is maintained. This preliminary study indicates passive heating is safe for the brain, at least in young healthy men.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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