Biomarkers of neuronal damage in saturation diving-a controlled observational study

Anders Rosén, Mikael Gennser, Nicklas Oscarsson, Andreas Kvarnström, Göran Sandström, Kaj Blennow, Helen Seeman-Lodding, Henrik Zetterberg, Anders Rosén, Mikael Gennser, Nicklas Oscarsson, Andreas Kvarnström, Göran Sandström, Kaj Blennow, Helen Seeman-Lodding, Henrik Zetterberg

Abstract

Purpose: A prospective and controlled observational study was performed to determine if the central nervous system injury markers glial fibrillary acidic protein (GFAp), neurofilament light (NfL) and tau concentrations changed in response to a saturation dive.

Methods: The intervention group consisted of 14 submariners compressed to 401 kPa in a dry hyperbaric chamber. They remained pressurized for 36 h and were then decompressed over 70 h. A control group of 12 individuals was used. Blood samples were obtained from both groups before, during and after hyperbaric exposure, and from the intervention group after a further 25-26 h.

Results: There were no statistically significant changes in the concentrations of GFAp, NfL and tau in the intervention group. During hyperbaric exposure, GFAp decreased in the control group (mean/median - 15.1/ - 8.9 pg·mL-1, p < 0.01) and there was a significant difference in absolute change of GFAp and NfL between the groups (17.7 pg·mL-1, p = 0.02 and 2.34 pg·mL-1, p = 0.02, respectively). Albumin decreased in the control group (mean/median - 2.74 g/L/ - 0.95 g/L, p = 0.02), but there was no statistically significant difference in albumin levels between the groups. In the intervention group, haematocrit and mean haemoglobin values were slightly increased after hyperbaric exposure (mean/median 2.3%/1.5%, p = 0.02 and 4.9 g/L, p = 0.06, respectively).

Conclusion: Hyperbaric exposure to 401 kPa for 36 h was not associated with significant increases in GFAp, NfL or tau concentrations. Albumin levels, changes in hydration or diurnal variation were unlikely to have confounded the results. Saturation exposure to 401 kPa seems to be a procedure not harmful to the central nervous system.

Trial registration: ClinicalTrials.gov NCT03192930.

Keywords: Biomarkers; Central nervous system; Diving; Neuronal damage; Saturation diving; hyperbaric.

Conflict of interest statement

HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).

Figures

Fig. 1
Fig. 1
GFAp levels (pg/mL) before, during and after hyperbaric exposure
Fig. 2
Fig. 2
NfL levels (pg/mL) before, during and after hyperbaric exposure
Fig. 3
Fig. 3
Tau levels (pg/mL) before, during and after hyperbaric exposure

References

    1. Andersen IB, Brasen CL, Christensen H, et al. Standardised testing time prior to blood sampling and diurnal variation associated with risk of patient misclassification: results from selected biochemical components. PLoS ONE. 2015;10(10):e0140475.
    1. Balestra C, Germonpré P. Correlation between patent foramen ovale, cerebral “lesions” and neuropsychometric testing in experienced sport divers: does diving damage the brain? Front Psychol. 2016;7:696.
    1. Bast-Petrersen R, Skare Ø, Nordby K-C, Skogstad M. A twelve-year longditudinal study of neuropsychological function in non-saturation professional divers. Int Arch Occup Environ Haelth. 2015;88(6):669–682.
    1. Bennet P, Rostain JC. Inert gas narcosis. In: Brubakk AO, Neumann TS, editors. Bennet and Elliot’s physiology and medicine of diving. 5. Philadelphia: Saunders; 2003. pp. 300–303.
    1. Brenner M. Role of GFAP in CNS injuries. Neurosci lett. 2014;565:7–13.
    1. Cordes P, Keil R, Bartsch T, et al. Neurologic outcome of compressed-air diving. Neurology. 2000;55:1743–1746.
    1. Edmonds C, Bennet M, Lippmann J, Mitchell SJ. Diving and subaquatic medicine. 5. Boca Raton: CRC Press; 2016. Oxygen toxicity; pp. 230–238.
    1. Edmonds C, Bennet M, Lippmann J, Mitchell SJ. Diving and subaquatic medicine. 5. Boca Raton: CRC Press; 2016. Carbon dioxide toxicity; pp. 245–254.
    1. Eftedal OS, Lydersen S, Brubakk AO. The relationship between gas bubbles and adverse effects of decompression after air dives. Undersea Hyperb Med. 2007;34(2):99–105.
    1. Evered L, Silbert B, Scott DA, Zetterberg H, Blennow K. Association of changes in plasma neurofilament light and tau levels with anesthesia and surgery. JAMANeurol. 2018;75(5):542–547.
    1. Femenia T, Gimenez-Cassina A, Codeluppi S, et al. Disrupted neuroglial metabolic coupling after peripheral surgery. J Neurosci. 2018;38(2):452–464.
    1. Foerch C, Niessner M, Back T, et al. Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral haemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem. 2012;58(1):237–245.
    1. Francis TJR, Mitchell SJ. Pathophysiology of decompression sickness. In: Brubakk AO, Neumann TS, editors. Bennet and Elliot’s physiology and medicine of diving. 5. Philadelphia: Saunders; 2003. pp. 531–544.
    1. Gennser M, Grönkvist M. Utprovning av mättnadsdekompressionstabell från grund luft- och nitroxmättnad. Stockholm, Sweden: Swedish Aerospace Physiology Centre, Department of Environmental Physiology, School of Chemistry, Biotechnology and Health, Royal Institute of Technology KTH; 2019.
    1. Germonpré P, Balestra C. Preconditioning to reduce decompression stress in scuba divers. Aerosp Med Hum Perform. 2017;88(2):114–120.
    1. Gill J, Latour L, Diaz-Arrastia R, et al. Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI. Neurology. 2018;91(15):e1385–e1389.
    1. Gren M, Shahim P, Lautner R, Wilson DH, Andreasson U, et al. Blood biomarkers indicate mild neuroaxonal injury and increased amyloid beta production after transient hypoxia during breath-hold diving. Brain Inj. 2016;30:1226–1230.
    1. Grønning M, Aarli JA. Neurological effects of deep diving. J Neurol Sci. 2011;304(1–2):17–21.
    1. Hamilton RW. Tolerating exposures to high oxygen levels. Repex and other methods. Mar Tech Soc J. 1989;23(4):19–25.
    1. Hemelryck W, Germonpre P, Papadopoulou V, Rozloznik M, Balestra C. Long term effects of recreational SCUBA diving on higher cognitive function. Scand J Med Sci Sports. 2014;24:928–934.
    1. Hofsø D, Ulvik RJ, Segadal K, Hope A, Thorsen E. Changes in erythropoietin and haemoglobin concentrations in response to saturation diving. Eur J Appl Physiol. 2005;95(2–3):191–196.
    1. Kahlil M, Teunissen CE, Otto M, Piehl F, Sormani MP, et al. Neurofilaments as biomarkers in neurological disorders. Neurology. 2018;14:577–589.
    1. Le Péchon JC, Gourdon G. Compressed-air work is entering the field of high pressures. Undersea Hyperb Med. 2010;37(4):193–198.
    1. Luczynski D, Lautridou J, Hjelde a, Monnoyer R, Eftedal I, Hemoglobin during and following a 4-week commercial saturation dive to 200 m. Front Physiol. 2019;10:1494.
    1. Matomäki P, Kainulainen H, Kyröläinen H. Corrected whole blood biomarkers – the equation of Dill and Costill revisited. Physiol Reports. 2018;6(12):e13749.
    1. Mattson N, Zetterberg H, Nielsen N, Blennow K, Dankiewicz J, et al. Serum tau and neurological outcome in cardiac arrest. Ann Neurol. 2017;82:665–675.
    1. Miller GD, Teramoto M, Smeal SJ, Cushman D, Eichner D. Assessing serum albumin concentration following exercise-induced fluid shifts in the context of the athlete biological passport. Drug test Anal. 2019;11(6):782–791.
    1. Neselius S, Brisby H, Theodorsson A, Blennow K, Zetterberg H, Marcusson J. CSF-biomarkers in Olympic boxing: Diagnosis and effects of repetitive head trauma. PLoS ONE. 2012;7(4):e33606.
    1. Nishi RY, Brubakk AO, Eftedal OS. Bubble detection. In: Brubakk AO, Neumann TS, editors. Bennet and Elliot’s physiology and medicine of diving. 5. Philadelphia: Saunders; 2003. pp. 517–520.
    1. Papadopoulou V, Germonpré P, Cosgrove D, et al. Variability in circulating gas emboli after a same scuba dive exposure. Eur Appl Physiol. 2018;118(6):1255–1264.
    1. Powell M. Deco for divers. 2. Southend-On-Sea: Aquapress; 2014. Saturation diving; pp. 89–94.
    1. Rosén A, Oscarsson N, Kvarnström A, Gennser M, Sandström G, et al. Serum tau concentration after diving – an observational pilot study. Diving Hyperb Med. 2019;49(2):88–95.
    1. Sato C, Barthélemy NR, Mawuenyega KG, et al. Tau kinetics in neurons and the human nervous system. Neuron. 2018;98(4):861–864.
    1. Sennels HP, Jørgensen HL, Hansen ALS, Goetze JP, Fahrenkrug J. Diurnal variation of hematology parameters in healthy young males: the Bispebjerg study of diurnal variations. Scand J Clin Lab Invest. 2011;71(7):532–541.
    1. Shahim P, Tegner Y, Wilson DH, Randall J, Skillbäck T, et al. Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurol. 2014;71:684–692.
    1. Shahim P, Arnell P, Kvarnström A, Rosén A, Bremell D, et al. Cerebrospinal fluid markers of central nervous system injury in decompression illness - a case-controlled pilot study. Diving Hyperb Med. 2015;45:240–243.
    1. Shahim P, Gren M, Liman V, Andreasson U, Norgren N, et al. Serum neurofilament light protein predicts clinical outcome in traumatic brain injury. Sci Rep. 2016;6:36791.
    1. Shahim P, Tegner Y, Marklund N, Blennow K, Zetterberg H. Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology. 2018;90(20):e1780–e1788.
    1. Slosman DO, de Ribaupierre S, Chichero C, et al. Negative neurofunctional effects of frequency, depth and environment in recreational SCUBA diving: the Geneva “memory dive” study. Br J Sports Med. 2004;38:108–114.
    1. Taylor CL, Macdiarmid JI, Ross JAS, et al. Objective neuropsychological test performance of professional divers reporting a subjective complaint of “forgetfulness or loss of concentration”. Scand J Work Environ Health. 2006;32(4):310–317.
    1. Todnem K, Nyland H, Kambestad BK, Aarli JA. Influence of occupational diving upon the nervous system: an epidemiological study. Br J Ind Med. 1990;47(10):708–714.
    1. Todnem K, Nyland H, Skeidsvoll H, Svihus R, Rinck P, et al. Neurological long term consequences of deep diving. Br J Ind Med. 1991;48:258–266.
    1. Wang YF, Hatton GI. Astrocytic plasticity and patterned oxycontin neuronal activity: dynamic interactions. J Neurosci. 2009;29(6):1743–1754.
    1. Zetterberg H, Blennow K. Fluid biomarkers for mild traumatic brain injury and related conditions. Nat Rev Neurol. 2016;12:563–574.
    1. Zetterberg H, Hietala A, Jonsson M, et al. Neurochemical aftermath of amateur boxing. Arch Neurol. 2006;63:1277–1280.

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