Gravitational transitions increase posterior cerebral perfusion and systemic oxidative-nitrosative stress: implications for neurovascular unit integrity

Damian Bailey, Damien Lanéelle, Jean-Eudes Trihan, Nicola Marchi, Benjamin Stacey, Kazuki Tamiya, Takuro Washio, Eduoard Tuaillon, Christoph Hirtz, Sylvain Lehmann, Shigehiko Ogoh, Hervé Normand

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    Abstract

    The present study examined if repeated bouts of micro- and hypergravity during parabolic flight (PF) alter structural integrity of the neurovascular unit (NVU) subsequent to free radical-mediated changes in regional cerebral perfusion. Six participants (5♂, 1♀) aged 29 ± 11 years were examined before, during and after a 3h PF and compared to six sex and age-matched (27 ± 6 years) normogravity controls. Blood flow was measured in the anterior (middle cerebral artery, MCA; internal carotid artery, ICA) and posterior (vertebral artery, VA) circulation (duplex ultrasound) in-flight over the course of 15 parabolas. Venous blood was assayed for free radicals (electron paramagnetic resonance spectroscopy), nitric oxide (NO, ozone-based chemiluminescence) and NVU integrity (chemiluminescence/ELISA) in normogravity before and after exposure to 31 parabolas. While MCA velocity did not change (P > 0.05), a selective increase in VA flow was observed during the most marked gravitational transition from micro- to hypergravity (P < 0.05). Increased oxidative-nitrosative stress defined by a free radical-mediated reduction in NO and elevations in glio-vascular GFAP and S100ß were observed after PF (P < 0.05), the latter proportional to the increase in VA flow (r = 0.908, P < 0.05). In contrast, biomarkers of neuronal-axonal damage (neuron-specific enolase, neurofilament light-chain, ubiquitin carboxy-terminal hydrolase L1 and tau) did not change (P > 0.05). Collectively, these findings suggest that the cumulative effects of repeated gravitational transitions may promote minor blood-brain barrier disruption, potentially related to the combined effects of haemodynamic (posterior cerebral hyperperfusion) and molecular (systemic oxidative-nitrosative) stress.
    Original languageEnglish
    Pages (from-to)142-160
    Number of pages19
    JournalNeuroscience
    Volume441
    Issue numberAugust 2020
    Early online date2 Jun 2020
    DOIs
    Publication statusPublished - 10 Aug 2020

    Keywords

    • blood–brain barrier
    • cerebral blood flow
    • free radicals
    • gravity
    • nitric oxide

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