Gravitational Transitions Increase Posterior Cerebral Perfusion and Systemic Oxidative-nitrosative Stress: Implications for Neurovascular Unit Integrity

Bailey, Damian Miles; Lanéelle, Damien; Trihan, Jean-Eudes; Marchi, Nicola; Stacey, Benjamin S.; Tamiya, Kazuki; Washio, Takuro; Tuaillon, Edouard; Hirtz, Christophe; Lehmann, Sylvain; Ogoh, Shigehiko; Normand, Hervé

doi:10.1016/j.neuroscience.2020.05.048

Cited by 9 publications

(10 citation statements)

References 79 publications

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“…The Peak Analysis package was used to calculate the area under the curve (mV/s) and subsequently converted to a concentration, using standard curves of known concentrations of sodium nitrite. 19 Intra-and inter-assay CVs were both <5%.…”

Section: Nitric Oxide Metabolitesmentioning

confidence: 97%

“…Twenty male professional rugby union players aged 25 (mean) ± 4 (SD) years were recruited from a professional rugby union first team. Players reported 3 (interquartile range [IQR], 1-4) concussions incurred over 16 (IQR, [13][14][15][16][17][18][19] years and were compared with 17 sex-, age-, physical activity-, and education-matched controls, with no participation in contact sports or concussion history (Table 1). All participants were free of disease, non-smokers and were not taking nutritional supplements or prescribed medication.…”

Section: Participants and Designmentioning

confidence: 99%

“…15 Players confirmed an average of 11 (IQR, 11-15) months since their most recent concussion. The average time between concussions was 16 (IQR, [13][14][15][16][17][18][19][20] months and return-to-play granted following 11 (IQR, 7-15) days. decline subsequent to prior-recurrent contact and concussion history is associated with a free radical-mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.…”

Section: Playersmentioning

confidence: 99%

“…21 Automated ELISA (LIAISON®, DiaSorin) and Single Molecule Array (Simoa) technology (Neuro 4-Plexassay kit, Quanterix TM ) determined serum concentrations of S100B/NSE and GFAP/NF-L/UCH-L1/tau, respectively. 19 This digital ELISA assay is considered ~500-1000-fold more sensitive than conventional immunoassays, with detection limits of 0.02 pg/ml. 22 All samples were analyzed using a fourfold dilution provided in the kit (phosphate buffer with bovine serum and heterophilic blocker solution) to minimize matrix effects.…”

Section: Neurovascular Unit Integritymentioning

confidence: 99%

See 3 more Smart Citations

Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition

Owens

Calverley

Stacey

et al. 2021

Scandinavian Med Sci Sports

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Section: Nitric Oxide Metabolitesmentioning

confidence: 97%

Section: Participants and Designmentioning

confidence: 99%

Section: Playersmentioning

confidence: 99%

Section: Neurovascular Unit Integritymentioning

confidence: 99%

See 2 more Smart Citations

Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition

Owens

Calverley

Stacey

et al. 2021

Scandinavian Med Sci Sports

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“…Given this knowledge and in contrast to what would be expected during steady-state CVR, we hypothesized that the onset of CBF response to changes in CO 2 (dynamic CVR) would be altered by gravitational stress subsequent to changes in the central respiratory chemoreflex ( Ogoh et al, 2009 ). Also, given the preferential defense of cerebral substrate delivery to the phylogenetically older, evolutionary conserved hindbrain (supplied by the posterior circulation; Bailey et al, 2020 ; Calverley et al, 2020 ), we further hypothesized that these interactive changes would be more pronounced in the anterior circulation subserved by the MCA. To test these hypotheses, the present study sought to characterize the onset responses of the respiratory chemoreflex and middle cerebral artery (MCA) and posterior cerebral artery (PCA) mean blood velocity (V mean ) to hypercapnia incorporating HUT-induced orthostasis as a terrestrial spaceflight analogue of gravitational stress.…”

Section: Introductionmentioning

confidence: 99%

Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

et al. 2022

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Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

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Blood Biomarkers May Have Found a New Frontier in Spaceflight—Reply

Eulenburg

2022

JAMA Neurol

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To the Editor We congratulate zu Eulenburg et al 1 for their longitudinal study of postspaceflight changes in blood-based biomarkers in 5 cosmonauts. Unlike a previous study, which used magnetic resonance imaging to evaluate the neurologic changes after spaceflight in cosmonauts, 2 blood-based biomarkers may present a practical breakthrough in monitoring neurologic health in real time in space on successful validation of the current findings. Their findings are remarkable in that several biomarkers (eg, neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], amyloid-β proteins 42 and 40) showed elevations postspaceflight compared with prespaceflight. However, there are several key limitations that we thought were worth highlighting to the JAMA Neurology readership.The sample size was small (n = 5), and results need to be replicated in a larger sample. However, the time-course patterns of select biomarkers showed an interesting quadratic trend, where most biomarkers peaked at 1 week postspaceflight and began returning to baseline level at 3 weeks postspaceflight. This pattern poses a question as to whether it is the long stay in space (average of 6 months) or the sudden change from microgravity in space to gravity on earth that triggers the elevations of blood biomarkers. If the former is correct, degenerative cellular responses to microgravity would have been progressive during the 6-month space mission, and biomarker levels at 1 day postspaceflight would have shown more remarkable changes from prespaceflight, instead of gradually increasing upon their return. The latter is also plausible because returning from space is a very stressful experience on the body, 3 possibly triggering an inflammatory response, and microstructural components of the brain must readapt to gravity on earth. Given that NfL and GFAP are sensitive to very mild subconcussive head impacts (eg, soccer heading), 4,5 their elevations may be due to the crossing effect of nongravity to gravity. Blood sampling during the space mission would have addressed this issue.It would also be paramount to understand why the biomarker time series of some individuals showed minimal from spaceflight whereas others exhibited continued elevation up to 3 weeks postspaceflight. A larger-scale multinational study in cosmonauts will allow stratification of additional factors, such as sex, age, genetic variance, years of spaceflight training, number of space missions, and any preexisting comorbidities. With plans for longer-duration spaceflights and recent developments in civilian access to space, delineating the neurologic consequences of spaceflight is critical, and we look forward to continued investigations of the effects of spaceflight on neurologic health using bloodbased biomarkers.

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Gravitational Transitions Increase Posterior Cerebral Perfusion and Systemic Oxidative-nitrosative Stress: Implications for Neurovascular Unit Integrity

Cited by 9 publications

References 79 publications

Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition

Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition

Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

Blood Biomarkers May Have Found a New Frontier in Spaceflight—Reply

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