SpringerLink
Log in

Brain interstitial glycerol correlates with evolving brain injury in paediatric traumatic brain injury

  • Original Article
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Purpose

A better understanding of the complex pathophysiology of traumatic brain injury (TBI) is needed to improve our current therapies. Cerebral microdialysis (CMD) is an advanced method to monitor the brain, but little is known about its parameters in children. Brain glycerol, one of the CMD variables, is an essential component of the phospholipid bilayer cell membrane and is considered a useful marker of tissue hypoxia in adults. This study examined the time course of glycerol and its associations in paediatric TBI.

Methods

In this retrospective cohort study, we collected data on children (< 13years) with severe TBI who underwent CMD monitoring. The relationship of glycerol was examined with respect to physiological, radiological variables, and clinical outcome.

Results

Twenty-eight children underwent CMD monitoring and had evaluable data. Lesion progression on head computed tomography (CT) demonstrated a strong relationship with glycerol (median glycerol, maximum and initial-to-maximum) when lesion size increased by > 30% (p=0.01, p=0.04 and p=0.004). Absolute glycerol values had a weak but statistically significant association with intracranial pressure and brain oxygenation. We did not find an association with clinical outcome.

Conclusion

This is the first study to provide data on brain interstitial glycerol in children. CMD glycerol, particularly an increase from baseline, is associated with other markers of injury and with a significant increase in lesion size on repeat head CT. As such, it may represent a useful monitorable marker for evolving injury in paediatric TBI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Belli A, Sen J, Petzold A, Russo S, Kitchen N, Smith M (2008) Metabolic failure precedes intracranial pressure rises in traumatic brain injury: A microdialysis study. Acta Neurochir 150:461–470

    Article  CAS  Google Scholar 

  2. Clausen T, Alves OL, Reinert M, Doppenberg E, Zauner A, Bullock R (2005) Association between elevated brain tissue glycerol levels and poor outcome following severe traumatic brain injury. J Neurosurg 103:233–238

    Article  CAS  Google Scholar 

  3. Dash PK, Zhao J, Hergenroeder G, Moore AN (2010) Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. Neurotherapeutics 7:100–114

    Article  CAS  Google Scholar 

  4. Dewan MC, Mummareddy N, Wellons JC III, Bonfield CM (2016) Epidemiology of global pediatric traumatic brain injury: Qualitative review. World Neurosurg 91:497–509

    Article  Google Scholar 

  5. Feala JD, AbdulHameed MDM, Yu C et al (2013) Systems biology approaches for discovering biomarkers for traumatic brain injury. J Neurotrauma 30:1101–1116

    Article  Google Scholar 

  6. Figaji AA, Zwane E, Fieggen AG, Argent AC, le Roux PD, Siesjo P, Peter JC (2009) Pressure autoregulation, intracranial pressure, and brain tissue oxygenation in children with severe traumatic brain injury. J Neurosurg Peds 4:420–428

    Article  Google Scholar 

  7. Figaji AA, Zwane E, Thompson C, Fieggen AG, Argent AC, le Roux PD, Peter JC (2009) Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury. Childs Nerv Syst 25:1325–1333

    Article  Google Scholar 

  8. Figaji AA (2017) Anatomical and physiological differences between children and adults relevant to traumatic brain injury and the implications for clinical assessment and care. Front Neurol 8:685

    Article  Google Scholar 

  9. Frykholm P, Hillered L, Långström B, Persson L, Valtysson J, Watanabe Y, Enblad P (2001) Increase of interstitial glycerol reflects the degree of ischaemic brain damage: A PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model. J Neurol Neurosurg Psychiatry 71:455–461

    Article  CAS  Google Scholar 

  10. Greve MW, Zink BJ (2009) Pathophysiology of traumatic brain injury. Mount Sinai J Med 76:97–104

    Article  Google Scholar 

  11. James SL, Theadom A, Ellenbogen RG et al (2019) Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 18:56–87

  12. Jones PA, Andrews PJ, Midgley S, Anderson SI, Piper IR, Tocher JL, Housley AM, Corrie JA, Slattery J, Dearden NM (1994) Measuring the burden of secondary insults in head-injured patients during intensive care. J Neurosurg Anesthesiol 6:4–14

    Article  CAS  Google Scholar 

  13. Kleinman ME, Chameides L, Schexnayder SM, Samson RA, Hazinski MF, Atkins DL, Berg MD, de Caen AR, Fink EL, Freid EB, Hickey RW, Marino BS, Nadkarni VM, Proctor LT, Qureshi FA, Sartorelli K, Topjian A, van der Jagt EW, Zaritsky AL (2010) Part 14: Pediatric advanced life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 122:S876–S908

    Article  Google Scholar 

  14. Maas AI, Hukkelhoven CW, Marshall LF et al (2005) 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 57:1173–1182

    Article  Google Scholar 

  15. Marklund N, Salci K, Lewén A, Hillered L (1997) Glycerol as a marker for post-traumatic membrane phospholipid degradation in rat brain. NeuroReport 8:1457–1460

    Article  CAS  Google Scholar 

  16. Mata-Mbemba D, Mugikura S, Nakagawa A, Murata T, Ishii K, Li L, Takase K, Kushimoto S, Takahashi S (2014) Early CT findings to predict early death in patients with traumatic brain injury: Marshall and Rotterdam CT scoring systems compared in the major academic tertiary care hospital in northeastern Japan. Acad Radiol 21:605–611

    Article  Google Scholar 

  17. Mellergård P, Sjögren F, Hillman J (2012) The cerebral extracellular release of glycerol, glutamate, and FGF2 is increased in older patients following severe traumatic brain injury. J Neurotrauma 29:112–118

    Article  Google Scholar 

  18. Merenda A, Gugliotta M, Holloway R, Levasseur JE, Alessandri B, Sun D, Bullock MR (2008) Validation of brain extracellular glycerol as an indicator of cellular membrane damage due to free radical activity after traumatic brain injury. J Neurotrauma 25:527–537

    Article  Google Scholar 

  19. Narayan RK, Maas AI, Servadei F et al (2008) Progression of traumatic intracerebral hemorrhage: a prospective observational study. J Neurotrauma 25:629–639

    Article  Google Scholar 

  20. Nilsson OG, Brandt L, Ungerstedt U, Säveland H (1999) Bedside detection of brain ischemia using intracerebral microdialysis: Subarachnoid hemorrhage and delayed ischemic deterioration. Neurosurgery 45:1176–1185

    Article  CAS  Google Scholar 

  21. Peerdeman SM, Girbes AR, Polderman KH et al (2003) Changes in cerebral interstitial glycerol concentration in head-injured patients; correlation with secondary events. Intensive Care Med 29:1825–1828

    Article  Google Scholar 

  22. Richards DA, Tolias CM, Sgouros S, Bowery NG (2003) Extracellular glutamine to glutamate ratio may predict outcome in the injured brain: a clinical microdialysis study in children. Pharmacol Res 48:101–109

    CAS  PubMed  Google Scholar 

  23. Roh D, Park S (2016) Brain multimodality monitoring: updated perspectives. Curr Neurol Neurosci Rep 16:56

    Article  Google Scholar 

  24. Rohlwink UK, Figaji AA (2010) Methods of monitoring brain oxygenation. Childs Nerv Syst 26:453–464

    Article  Google Scholar 

  25. Rubiano AM, Carney N, Chesnut R, Puyana JC (2015) Global neurotrauma research challenges and opportunities. Nature 527:S193–S197

    Article  CAS  Google Scholar 

  26. Schulz MK, Wang LP, Tange M, Bjerre P (2000) Cerebral microdialysis monitoring: determination of normal and ischemic cerebral metabolisms in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 93:808–814

    Article  CAS  Google Scholar 

  27. Ståhl N, Mellergård P, Hallström A, Ungerstedt U, Nordström CH (2001) Intracerebral microdialysis and bedside biochemical analysis in patients with fatal traumatic brain lesions. Acta Anaesthesiol Scand 45:977–985

    Article  Google Scholar 

  28. Tisdall MM, Smith M (2006) Cerebral microdialysis: research technique or clinical tool. Brit J Anesthesia 97:18–25

    Article  CAS  Google Scholar 

  29. Tolias CM, Richards DA, Bowery NG et al (2002) Extracellular glutamate in the brains of children with severe head injuries: a pilot microdialysis study. Childs Nerv Syst 18:368–374

    PubMed  Google Scholar 

  30. Vespa PM, Martin NA, Nenov V, Glenn T, Bergsneider M, Kelly D, Becker DP, Hovda DA (2002) Delayed increase in extracellular glycerol with Post–Traumatic electrographic epileptic activity: support for the theory that seizures induce secondary injury. In: Intracranial Pressure and Brain Biochemical Monitoring, Acta Neurochirurgica Supplements, vol 81. Springer, Vienna, pp 355–357

    Chapter  Google Scholar 

  31. World Health Organization (2006) Neurological disorders: public health challenges. WHO Press, Geneva

Download references

Acknowledgements

The authors would like to thank Prof Peter Siesjo and Dr David Cederberg from Lund University for their valuable assistance in the initial setup of microdialysis monitoring at our institution. Their help was greatly appreciated.

Funding

Dr Thango received a bursary from the National Research Foundation. Anthony Figaji is supported by the NRF SARChI Chair of Clinical Neurosciences. We gratefully acknowledge the effort of the neurosurgical residents in contributing to the success of the project.

Author information

Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa

    Nqobile S. Thango, Ursula K. Rohlwink, Lindizwe Dlamini, M. Phophi Tshavhungwe, J.M.N. Enslin & Anthony A. Figaji

  2. Neuroscience Institute, University of Cape Town, Cape Town, South Africa

    Ursula K. Rohlwink & Anthony A. Figaji

  3. Department of Radiology, University of Cape Town, Cape Town, South Africa

    E. Banderker

  4. Paediatric Intensive Care Unit, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa

    Shamiel Salie

Authors
  1. Nqobile S. Thango
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ursula K. Rohlwink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lindizwe Dlamini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Phophi Tshavhungwe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Banderker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shamiel Salie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J.M.N. Enslin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anthony A. Figaji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anthony A. Figaji.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thango, N.S., Rohlwink, U.K., Dlamini, L. et al. Brain interstitial glycerol correlates with evolving brain injury in paediatric traumatic brain injury. Childs Nerv Syst 37, 1713–1721 (2021). https://doi.org/10.1007/s00381-021-05058-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-021-05058-2

Keywords

Search

Navigation