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Research ArticleResearch Article: New Research, Disorders of the Nervous System

Release of Extracellular Matrix Components after Human Traumatic Brain Injury

Michael Bambrick, Deena Godfrey, Mark D. Johnson, Jeffrey D. Esko, Biswa Choudhury, Alejandro Gomez Toledo, Mousumi Paulchakrabarti, Carla Fortes, Kevin J. Staley and Ann-Christine Duhaime
eNeuro 10 June 2025, 12 (6) ENEURO.0488-24.2025; https://doi.org/10.1523/ENEURO.0488-24.2025
Michael Bambrick
1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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Deena Godfrey
2Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, Massachusetts 02129
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  • ORCID record for Deena Godfrey
Mark D. Johnson
3Department of Neurosurgery, University of Massachusetts Memorial Health, University of Massachusetts Chan Medical School, Worcester, Massachusetts 01655
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Jeffrey D. Esko
4Department of Cellular and Molecular Medicine, University of California, San Diego Medical School, La Jolla, California 92093
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Biswa Choudhury
4Department of Cellular and Molecular Medicine, University of California, San Diego Medical School, La Jolla, California 92093
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Alejandro Gomez Toledo
4Department of Cellular and Molecular Medicine, University of California, San Diego Medical School, La Jolla, California 92093
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Mousumi Paulchakrabarti
4Department of Cellular and Molecular Medicine, University of California, San Diego Medical School, La Jolla, California 92093
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Carla Fortes
1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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Kevin J. Staley
5Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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Ann-Christine Duhaime
1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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Article Figures & Data

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  • Figure 1.
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    Figure 1.

    Proteoglycans and sulfated glycosaminoglycans. Proteoglycans consist of a protein core (brown) and one or more covalently attached glycosaminoglycan chains (dark blue, HS, heparan sulfate; yellow, CS/DS, chondroitin sulfate/dermatan sulfate; light blue, KS, keratan sulfate). Membrane proteoglycans either span the plasma membrane (Type I membrane proteins) or are linked by a glycosylphosphatidylinositol (GPI) anchor. Extracellular matrix proteoglycans are usually secreted, but some proteoglycans can be proteolytically cleaved and shed from the cell surface (data not shown). Reprinted with permission from Merry et al. (2022). HS, heparan sulfate, CS/DS, chondroitin sulfate/dermatan sulfate, KS, keratan sulfate.

  • Figure 2.
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    Figure 2.

    CSF chondroitin sulfate disaccharide concentration. Concentration of chondroitin sulfate disaccharides within cerebrospinal fluid samples. Concentration is measured in ng/ml with D0a4/D2a0 disaccharide showing the highest average concentration and a statistically significant difference from the rest of the disaccharides (p < 0.005).

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    Figure 3.

    CSF heparan sulfate disaccharide concentration. Concentration of heparan sulfate disaccharides in CSF samples. Concentrations are measured in ng/ml with the D0A0 disaccharide having the highest mean concentration and statistically significant value compared with the rest of the disaccharides (p < 0.0005).

  • Figure 4.
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    Figure 4.

    CSF versus plasma chondroitin sulfate concentration. Plasma and CSF sGAG concentrations (ng/ml) of chondroitin sulfate plotted against one another and separated into groups denoting isolated head trauma or multitrauma. No correlation was observed either within the groups or between the groups. The linear regression of each of the individual groups was also not found to be significant. Blue represents isolated head trauma, orange represents multitrauma.

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    Figure 5.

    CSF versus plasma heparan sulfate concentration. Plasma and CSF sGAG concentrations (ng/ml) of heparan sulfate plotted against one another and separated into groups denoting isolated head trauma or multitrauma. No correlation was observed either within the groups or between the groups. The linear regression of each of the individual groups was also not found to be significant. While plasma levels on average were higher in multitrauma patients compared with those with isolated head injury, these differences were not significant. Blue represents isolated head trauma, orange represents multitrauma.

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    Figure 6.

    Distance from lateral ventricle compared with heparan sulfate sGAG concentration. Heparan sulfate concentration in CSF samples plotted against distance from the lateral ventricle where the external ventricular drain was placed. Pearson’s correlation was found to be −0.75 with a p-value of 0.048. This effect was not found in chondroitin sulfate CSF samples.

Tables

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    Table 1.

    Image “injury load” scoring system

    Imaging featureScoringRange of points
    Extradural injury (skull fracture or hematoma)Absent = 0, present = 10–1
    Supratentorial parenchymal hemorrhage1 point for present in each lobe (right and left)0–8
    Subdural and/or subarachnoid hemorrhage1 point for present over each lobe (right and left)0–8
    Posterior fossa hemorrhage (parenchymal, subdural, or subarachnoid)1 point if 1–2 cm, 2 points if larger0–2
    Intraventricular hemorrhage >5 mm1 point0–1
    Midline shift >1 cm1 point0–1
    Total possible points0–21
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    Table 2.

    Time (hours) from injury to first CSF sample collection for 9 subjects from Site 1

    SubjectTime from Injury (hours)
    171.98
    246.83
    338.43
    464.38
    570.07
    685.95
    789.58
    886.83
    9115.05
    Mean (SD)74.35 (23.32)
    • Time from injury to initial CSF sample collection. Specific timing data available for 9 of the 10 subjects recruited from Site 1. CSF, cerebrospinal fluid; SD, standard deviation.

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    Table 3.

    Chondroitin sulfate disaccharide concentrations (ng/ml) in CSF of 11 subjects

    01-0101-0201-0301-0401-0501-0601-0701-0802-0102-0202-03Mean
    D0a031.8715.7868.893.6814.29111.698.3635.4130.0810.619.1230.89
    D0a4/D2a0144.3073.04341.6517.77128.07506.2658.97144.81165.91115.5876.32161.15
    D0a622.747.5051.831.0521.3934.1316.5953.3154.488.598.6425.48
    D2a42.631.204.100.171.865.640.882.322.365.171.702.55
    D2a61.820.612.700.021.975.950.942.322.202.617.282.58
    D0a109.424.6219.491.117.1928.713.4910.7816.835.196.1410.27
    D2a100.030.000.000.000.000.140.000.040.070.040.010.03
    • Chondroitin sulfate disaccharide concentrations in CSF of 11 subjects [8 subjects from Site 1 (01-xx) and 3 subjects from Site 2 (02-xx)]. Three subject samples are not individually available for inclusion in this table but are incorporated into Figure 2.

    • View popup
    Table 4.

    Heparan sulfate disaccharide concentrations (ng/ml) in CSF of 11 subjects

    01-0101-0201-0301-0401-0501-0601-0701-0802-0102-0202-03Mean
    D0H00.070.000.000.000.030.580.000.020.370.060.000.10
    D0A020.053.1636.081.6020.8233.998.6217.9833.3616.6211.2018.50
    D0H60.000.000.000.000.000.010.010.000.000.000.000.00
    D2H00.000.000.000.000.000.000.000.010.000.000.000.00
    D0S05.122.008.820.225.558.072.384.337.974.042.894.67
    D0A64.281.405.710.172.914.261.192.162.902.481.832.66
    D2A00.240.020.270.000.410.530.180.220.350.510.270.27
    D2H60.000.000.000.000.330.480.060.040.310.400.230.17
    D0S61.030.080.960.002.362.790.721.041.622.371.331.30
    D2S03.621.324.580.1010.615.331.501.803.623.862.583.54
    D2A60.000.000.000.000.010.010.000.010.000.020.000.00
    D2S61.990.542.660.002.502.450.661.781.572.341.361.62
    • Heparan sulfate disaccharide concentrations in CSF of 11 subjects [8 subjects from Site 1 (01-xx) and 3 subjects from Site 2 (02-xx)]. Three subject samples are not individually available for inclusion in this table but are incorporated into Figure 3.

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Release of Extracellular Matrix Components after Human Traumatic Brain Injury
Michael Bambrick, Deena Godfrey, Mark D. Johnson, Jeffrey D. Esko, Biswa Choudhury, Alejandro Gomez Toledo, Mousumi Paulchakrabarti, Carla Fortes, Kevin J. Staley, Ann-Christine Duhaime
eNeuro 10 June 2025, 12 (6) ENEURO.0488-24.2025; DOI: 10.1523/ENEURO.0488-24.2025

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Release of Extracellular Matrix Components after Human Traumatic Brain Injury
Michael Bambrick, Deena Godfrey, Mark D. Johnson, Jeffrey D. Esko, Biswa Choudhury, Alejandro Gomez Toledo, Mousumi Paulchakrabarti, Carla Fortes, Kevin J. Staley, Ann-Christine Duhaime
eNeuro 10 June 2025, 12 (6) ENEURO.0488-24.2025; DOI: 10.1523/ENEURO.0488-24.2025
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Keywords

  • cerebral spinal fluid
  • extracellular matrix
  • sulfated glycosaminoglycans
  • traumatic brain injury

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