Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage

Linda Hägglund, Magnus Olivecrona, Lars-Owe D Koskinen, Linda Hägglund, Magnus Olivecrona, Lars-Owe D Koskinen

Abstract

Background: This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored.

Methods: Patients with sTBI aged 15-70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE.

Results: In 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score.

Conclusions: We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood-brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.

Trial registration: ClinicalTrials.gov NCT01363583.

Keywords: Brain computed tomography; Glycerol; Microdialysis; Neuron-specific enolase; Outcome; S-100B; Traumatic brain injury.

Conflict of interest statement

The authors declare no conflict of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
A schematic presentation of the inclusion and exclusion of the patients. CPP cerebral perfusion pressure, GCS Glasgow Coma Scale Score
Fig. 2
Fig. 2
Bar plot of the regression plot slope coefficient between brain and subcutaneous glycerol in the total group and groups with a positive or negative correlation. Two-tailed unpaired t-test
Fig. 3
Fig. 3
Bar plot of the levels of the biochemical biomarkers in relation to the regression plot slope coefficient between brain and subcutaneous glycerol in the groups with a positive or negative correlation. Observe that the S-100B values are × 10 for visibility. Two-tailed unpaired t-test. NSEAUC bulk release of neuron-specific enolase, NSEmax maximal level of neuron-specific enolase, S-100BAUC bulk release of S-100B, S-100Bmax maximal level of S-100B

References

    1. Sundstrom T, Sollid S, Wentzel-Larsen T, Wester K. Head injury mortality in the Nordic countries. J Neurotrauma. 2007;24(1):147–153. doi: 10.1089/neu.2006.0099.
    1. Pedersen K, Fahlstedt M, Jacobsson A, Kleiven S, von Holst H. A National survey of traumatic brain injuries admitted to hospitals in Sweden from 1987 to 2010. Neuroepidemiology. 2015;45(1):20–27. doi: 10.1159/000381780.
    1. Steyerberg EW, Wiegers E, Sewalt C, et al. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019;18(10):923–934. doi: 10.1016/S1474-4422(19)30232-7.
    1. Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987–1048. doi: 10.1016/S1474-4422(17)30371-X.
    1. Merenda A, Gugliotta M, Holloway R, et al. Validation of brain extracellular glycerol as an indicator of cellular membrane damage due to free radical activity after traumatic brain injury. J Neurotrauma. 2008;25(5):527–537. doi: 10.1089/neu.2007.0359.
    1. Jungner M, Siemund R, Venturoli D, et al. Blood-brain barrier permeability following traumatic brain injury. Minerva Anestesiol. 2016;82(5):525–533.
    1. Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Blood-brain barrier: from physiology to disease and back. Physiol Rev. 2019;99(1):21–78. doi: 10.1152/physrev.00050.2017.
    1. Meyer JS, Itoh Y, Okamoto S, et al. Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. Circulation. 1975;51(4):701–712. doi: 10.1161/01.CIR.51.4.701.
    1. Rapoport SI. Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications. Cell Mol Neurobiol. 2000;20(2):217–230. doi: 10.1023/A:1007049806660.
    1. Mondello S, Sorinola A, Czeiter E, et al. Blood-based protein biomarkers for the management of traumatic brain injuries in adults presenting to emergency departments with mild brain injury: A living systematic review and meta-analysis. J Neurotrauma. 2021;38(8):1086–1106. doi: 10.1089/neu.2017.5182.
    1. Olivecrona M, Rodling-Wahlström M, Naredi S, Koskinen LO. S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy. J Neurol Neurosurg Psychiatry. 2009;80(11):1241–1247. doi: 10.1136/jnnp.2008.158196.
    1. Gao J, Zheng Z. Development of prognostic models for patients with traumatic brain injury: a systematic review. Int J Clin Exp Med. 2015;8(11):19881–19885.
    1. Grande PO. Critical evaluation of the Lund concept for treatment of severe traumatic head injury, 25 years after its introduction. Front Neurol. 2017;8:315. doi: 10.3389/fneur.2017.00315.
    1. Koskinen LO, Olivecrona M, Grande PO. Severe traumatic brain injury management and clinical outcome using the Lund concept. Neuroscience. 2014;283:245–255. doi: 10.1016/j.neuroscience.2014.06.039.
    1. Olivecrona M, Rodling-Wahlstrom M, Naredi S, Koskinen LO. Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study. J Neurotrauma. 2009;26(8):1251–1262. doi: 10.1089/neu.2008.0605.
    1. Olivecrona Z, Bobinski L, Koskinen LO. Association of ICP, CPP, CT findings and S-100B and NSE in severe traumatic head injury. Prognostic value of the biomarkers. Brain Inj. 2015;29(4):446–454. doi: 10.3109/02699052.2014.989403.
    1. Bobinski L, Olivecrona M, Koskinen LO. Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study. Acta Neurochir (Wien) 2012;154(6):1069–1079. doi: 10.1007/s00701-012-1345-x.
    1. Maas AI, Hukkelhoven CW, Marshall LF, Steyerberg EW. Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery. 2005;57(6):1173–1182. doi: 10.1227/01.NEU.0000186013.63046.6B.
    1. Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998;15(8):573–585. doi: 10.1089/neu.1998.15.573.
    1. Jansson PA, Larsson A, Smith U, Lönnroth P. Glycerol production in subcutaneous adipose tissue in lean and obese humans. J Clin Invest. 1992;89(5):1610–1617. doi: 10.1172/JCI115756.
    1. Koskinen LO, Eklund A, Sundstrom N, Olivecrona M. Prostacyclin influences the pressure reactivity in patients with severe traumatic brain injury treated with an ICP-targeted therapy. Neurocrit Care. 2015;22(1):26–33. doi: 10.1007/s12028-014-0030-8.
    1. Koskinen LD, Sundstrom N, Hagglund L, Eklund A, Olivecrona M. Prostacyclin affects the relation between brain interstitial glycerol and cerebrovascular pressure reactivity in severe traumatic brain injury. Neurocrit Care. 2019;31(3):494–500. doi: 10.1007/s12028-019-00741-4.
    1. Berger C, Sakowitz OW, Kiening KL, Schwab S. Neurochemical monitoring of glycerol therapy in patients with ischemic brain edema. Stroke. 2005;36(2):e4–6. doi: 10.1161/01.STR.0000151328.70519.e9.

Source: PubMed

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