Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children

Abstract

Background and Aims

Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions—as in major neurosurgical procedures—eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children.

Methods

Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6–74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines.

Results

An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2–5.5 d.), and postoperative ventilation need was 24 h (IQL range 20–61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded.

Conclusions

Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

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References

  1. 1.

    Deletis V, Sala F. The role of intraoperative neurophysiology in the protection or documentation of surgically induced injury to the spinal cord. Ann N Y Acad Sci. 2001;939:137–44.

    CAS  Article  Google Scholar 

  2. 2.

    Piastra M, Di Rocco C, Caresta E, et al. Blood loss and short-term outcome of infants undergoing brain tumour removal. J Neurooncol. 2008;90:191–200.

    Article  Google Scholar 

  3. 3.

    Borg A, Kirkman MA, Choi D. Endoscopic endonasal anterior skull base surgery: a systematic review of complications over the past 65 years. World Neurosurg. 2016;95:383–91.

    Article  Google Scholar 

  4. 4.

    Jadhav V, Solaroglu I, Obenaus A, et al. Neuroprotection against surgically induced brain injury. Surg Neurol. 2007;67:15–20.

    Article  Google Scholar 

  5. 5.

    Sherchan P, Kim CH, Zhang JH. Surgical brain injury and edema prevention. Acta Neurochir. 2013;118:129–33.

    Google Scholar 

  6. 6.

    Caresta E, Pierro A, Chowdhury M, et al. Oxidation of intravenous lipid in infants and children with systemic inflammatory response syndrome and sepsis. Pediatr Res. 2007;61:228–32.

    CAS  Article  Google Scholar 

  7. 7.

    Omaye ST, Turnbull JD, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol. 1979;62:3–11.

    CAS  Article  Google Scholar 

  8. 8.

    O’Shaughnessy DF, Atterbury C, Bolton MP, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol. 2004;126:11–28.

    Article  Google Scholar 

  9. 9.

    Piastra M, Pizza A, Tosi F, et al. Validation of the Glycemic Stress Index in pediatric neurosurgical intensive care. Neurocrit Care. 2017;26:388–92.

    CAS  Article  Google Scholar 

  10. 10.

    Pietrini D, Di Rocco C, Di Bartolomeo R, et al. No-glucose strategy influences posterior cranial fossa tumors’ postoperative course: introducing the Glycemic Stress Index. J Neurooncol. 2009;93:361–8.

    Article  Google Scholar 

  11. 11.

    Ayer RE, Zhang JH. Oxydative stress in subarachnoid hemorrhage: significance in acute brain injury and vasospasm. Acta Neurochir Suppl. 2008;104:33–41.

    CAS  Article  Google Scholar 

  12. 12.

    Srivastava R, Lohokare R, Prasad R. Oxidative stress in children with bacterial meningitis. J Trop Pediatr. 2013;59:305–8.

    Article  Google Scholar 

  13. 13.

    Kastenbauer S, Koedel U, Becker BF, et al. Oxidative stress in bacterial meningitis in humans. Neurology. 2002;58:186–91.

    CAS  Article  Google Scholar 

  14. 14.

    Bayir H, Kagan VE, Tyurina YY, et al. Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Res. 2002;51:571–8.

    Article  Google Scholar 

  15. 15.

    Cristofori L, Tavazzi B, Gambin R, et al. Early onset of lipid peroxidation after human traumatic brain injury: a fatal limitation for the free radical scavenger pharmacological therapy? J Investig Med. 2001;49:450–8.

    CAS  Article  Google Scholar 

  16. 16.

    Lewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma. 2000;17:871–90.

    CAS  Article  Google Scholar 

  17. 17.

    Inci S, Ozcan OE, Kilinç K. Time-level relationship for lipid peroxidation and the protective effect of alpha-tocopherol in experimental mild and severe brain injury. Neurosurgery. 1998;43:330–5.

    CAS  Article  Google Scholar 

  18. 18.

    Cirak B, Rousan N, Kocak A, Palaoglu O, Palaoglu S, Kilic K. Melatonin as a free radical scavenger in experimental head trauma. Pediatr Neurosurg. 1999;31(6):298–301.

    CAS  Article  Google Scholar 

  19. 19.

    Bayır H, Adelson PD, Wisniewski SR, et al. Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children. Crit Care Med. 2009;37:689–95.

    Article  Google Scholar 

  20. 20.

    Zengin E, Atukeren P, Kokoglu E, et al. Alterations in lipid peroxidation and antioxidant status in different types of intracranial tumors within their relative peritumoral tissues. Clin Neurol Neurosurg. 2009;111:345–51.

    Article  Google Scholar 

  21. 21.

    Pervaiz S, Clement MV. Tumor intracellular redox status and drug resistance— serendipity or a causal relationship? Curr Pharm Des. 2004;10:1969–77.

    CAS  Article  Google Scholar 

  22. 22.

    Yilmaz N, Dulger H, Kiymaz N, et al. Lipid peroxidation in patients with brain tumor. Int J Neurosci. 2006;116:937–43.

    CAS  Article  Google Scholar 

  23. 23.

    Bujok G, Dyaczyńska-Herman A, Jendryczko A, et al. Concentration of malonic dialdehyde in the cerebrospinal fluid as a measure of the intensity of lipid peroxidation processes in intracranial hypertension in small children. Childs Nerv Syst. 1996;12:97–9.

    CAS  Article  Google Scholar 

  24. 24.

    Spentzas T, Escue JE, Patters AB, et al. Brain tumor resection in children: neurointensive care unit course and resource utilization. Pediatr Crit Care Med. 2010;11:718–22.

    Article  Google Scholar 

  25. 25.

    Veluyatham PK, et al. Oxidative stress-associated hypertension in surgically induced brain injury patients: effects of β-blocker and angiotensin-converting enzyme inhibitor. J Surg Res. 2013;179:125–31.

    Article  Google Scholar 

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Authors

Contributions

Marco Piastra MD (M.P.), Elena Caresta MD (E.C.), Giorgio Conti MD (G.C.), and Simon Eaton MD (S.E.) designed the study, analyzed the data, and wrote the first draft of the paper; designed the study and wrote the first draft of the paper; Luca Massimi MD (L.M.), Enzo Picconi MD (E.P.), and Ersilia Luca MD (E.L.) recruited the patients and collected the data; Tony Christian Morena MD (T.C.M.) is the corresponding author, and also recruited the patients and collected the data.

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Correspondence to T. C. Morena.

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The study was approved by the Institutional Review Board of the Universita Cattolica del Sacro Cuore. Participation in the survey implies informed consent from the participants.

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Piastra, M., Caresta, E., Massimi, L. et al. Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children. Neurocrit Care 33, 124–131 (2020). https://doi.org/10.1007/s12028-019-00870-w

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Keywords

  • Pediatric neurosurgery
  • Pediatric intensive care
  • Antioxidant activity
  • Lipid peroxidation
  • Brain injury