Skip to main content
SpringerLink
Log in

MiRNA-124a: a Potential Biomarker for Neurological Deficits Following Cardiac Surgery in Pediatric Patients

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Brain injury is a major source of patient morbidity after cardiac surgery in children. New early accurate biomarkers are needed for the diagnosis of patients at risk for cerebral postoperative damage. Specific circulating miRNAs have been found as suitable biomarkers for many diseases. We tested whether miRNA-124a reflects neurological injury in pediatric patients following heart surgery. Serum samples were obtained from 34 patients before and six hours after heart surgery. MiRNAs-124a was quantified by RQ-PCR. MiRNA-124a levels six hours after heart surgery correlated with the neurological outcome of the patients. In children with neurological deficits, miRNA-124a levels increased while in those with no neurological deficits the levels decreased. MiRNA-124a was able, at six hours after the operation, to identify patients who are at risk for the appearance of neurological deficits. Circulating miRNA-124a is a potential biomarker for the appearance of neurological deficits in pediatric patients following heart surgery.

Graphical Abstract

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CHD:

congenital heart disease

MiRNA:

micro-RNA

CRP:

C-reactive protein

CPB:

cardiopulmonary bypass

ACC:

aortic crossclamp

ECMO:

extracorporeal membrane oxygenation

PSOM:

pediatric stroke outcome measure

GCS:

Glasgow Coma Scale

POCD:

postoperative cognitive dysfunction

NSE:

neuron-specific enolase

HIE:

hypoxic ischemic encephalopathy

RACHS:

Risk-Adjusted Classification for Congenital Heart Surgery

References

  1. Hogue Jr., C. W., Palin, C. A., & Arrowsmith, J. E. (2006). Cardiopulmonary bypass management and neurologic outcomes: An evidence-based appraisal of current practices. Anesthesia and Analgesia, 103(1), 21–37.

    Article  PubMed  Google Scholar 

  2. Dexheimer, P. J., & Cochella, L. (2020). MicroRNAs: From mechanism to organism. Frontiers in Cell and Development Biology, 8, 409.

    Article  Google Scholar 

  3. Nik Mohamed Kamal, N., & Shahidan, W. N. S. (2019). Non-exosomal and exosomal circulatory microRNAs: which are more valid as biomarkers? Frontiers in Pharmacology, 10, 1500.

    Article  PubMed  Google Scholar 

  4. Gareev, I., et al. (2020). The current state of MiRNAs as biomarkers and therapeutic tools. Clinical and Experimental Medicine, 20(3), 349–359.

    Article  CAS  PubMed  Google Scholar 

  5. Polito, F., et al. (2020). Circulating miRNAs expression as potential biomarkers of mild traumatic brain injury. Molecular Biology Reports, 47(4), 2941–2949.

    Article  CAS  PubMed  Google Scholar 

  6. Kozuka, T., et al. (2019). miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation. Scientific Reports, 9(1), 3445.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sun, Y., et al. (2015). An updated role of microRNA-124 in central nervous system disorders: A review. Frontiers in Cellular Neuroscience, 9, 193.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Beslow, L. A., et al. (2010). Predictors of outcome in childhood intracerebral hemorrhage: A prospective consecutive cohort study. Stroke, 41(2), 313–318.

    Article  PubMed  Google Scholar 

  9. Kitchen, L., et al. (2012). The pediatric stroke outcome measure: A validation and reliability study. Stroke, 43(6), 1602–1608.

    Article  PubMed  Google Scholar 

  10. Bar-Yosef, O., et al. (2018). Neurological deficit is predicted by S100B in children after cardiac surgery. Clinica Chimica Acta, 481, 56–60.

    Article  CAS  Google Scholar 

  11. Martinez, B., & Peplow, P. V. (2017). MicroRNAs as diagnostic markers and therapeutic targets for traumatic brain injury. Neural Regeneration Research, 12(11), 1749–1761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Devaux, Y., et al. (2016). Association of circulating microRNA-124-3p levels with outcomes after out-of-hospital cardiac arrest: A substudy of a randomized clinical trial. JAMA Cardiology, 1(3), 305–313.

    Article  PubMed  Google Scholar 

  13. Gilje, P., et al. (2014). The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest. Critical Care, 18(2), R40.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Albers, E. L., Bichell, D. P., & McLaughlin, B. (2010). New approaches to neuroprotection in infant heart surgery. Pediatric Research, 68(1), 1–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Andresen, M., et al. (2015). Therapeutic hypothermia for acute brain injuries. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 23, 42.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gancia, P., & Pomero, G. (2010). Brain cooling therapy. Minerva Pediatrica, 62(3 Suppl 1), 173–175.

    CAS  PubMed  Google Scholar 

  17. Devaux, Y., et al. (2017). Incremental value of circulating MiR-122-5p to predict outcome after out of hospital cardiac arrest. Theranostics, 7(10), 2555–2564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gan, C. S., Wang, C. W., & Tan, K. S. (2012). Circulatory microRNA-145 expression is increased in cerebral ischemia. Genetics and Molecular Research, 11(1), 147–152.

    Article  CAS  PubMed  Google Scholar 

  19. Kanninen, K. M., et al. (2016). Exosomes as new diagnostic tools in CNS diseases. Biochimica et Biophysica Acta, 1862(3), 403–410.

    Article  CAS  PubMed  Google Scholar 

  20. Veremeyko, T., et al. (2019). Neuronal extracellular microRNAs miR-124 and miR-9 mediate cell-cell communication between neurons and microglia. Journal of Neuroscience Research, 97(2), 162–184.

    Article  CAS  PubMed  Google Scholar 

  21. Grapp, M., et al. (2013). Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. Nature Communications, 4, 2123.

    Article  PubMed  Google Scholar 

  22. van den Berg, M. M. J., et al. (2020). Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders. Progress in Neurobiology, 185, 101732.

    Article  PubMed  Google Scholar 

  23. Straumfors, A., et al. (2020). Circulating miRNAs as molecular markers of occupational grain dust exposure. Scientific Reports, 10(1), 11317.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Seco, M., et al. (2012). Serum biomarkers of neurologic injury in cardiac operations. The Annals of Thoracic Surgery, 94(3), 1026–1033.

    Article  PubMed  Google Scholar 

  25. Varrica, A., et al. (2015). Circulating S100B and adiponectin in children who underwent open heart surgery and cardiopulmonary bypass. BioMed Research International, 2015, 402642.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sahutoglu, C., et al. (2018). Correlation between serum lactate levels and outcome in pediatric patients undergoing congenital heart surgery. Turk Gogus Kalp Damar Cerrahisi Derg, 26(3), 375–385.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Molina Hazan, V., et al. (2010). Blood lactate levels differ significantly between surviving and nonsurviving patients within the same risk-adjusted classification for congenital heart surgery (RACHS-1) group after pediatric cardiac surgery. Pediatric Cardiology, 31(7), 952–960.

    Article  PubMed  Google Scholar 

  28. Hanna, J., Hossain, G. S., & Kocerha, J. (2019). The potential for microRNA therapeutics and clinical research. Frontiers in Genetics, 10, 478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. McDonagh, D. L., et al. (2014). Neurological complications of cardiac surgery. Lancet Neurology, 13(5), 490–502.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Amisragas for their continuous support of the Department of Intensive Care. This study was performed at the Department of Pediatric Critical Care Medicine, Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel.

Funding

This work was funded with institutional departmental funds.

Author information

Author notes

  1. Gideon Paret and Yael Nevo-Caspi contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Critical Care Medicine, Safra Children’s Hospital, Sheba Medical Center, Israel, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Keren Zloto, Liat Mor, Gideon Paret & Yael Nevo-Caspi

  2. Department of Pediatric Neurology Unit, Safra Children’s Hospital, Sheba Medical Center, Israel, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Omer Bar-Yosef

  3. Department of Pediatric Cardiology, Safra Children’s Hospital, Sheba Medical Center, Israel, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Tal Tirosh-Wagner

  4. Department of Pediatric Cardiac Intensive Care, Safra Children’s Hospital, Sheba Medical Center, Israel, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Amir Vardi

  5. Department of Pediatric Cardiac Surgery, Safra Children’s Hospital, Sheba Medical Center, Israel, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    David Mishali

Authors
  1. Keren Zloto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liat Mor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Omer Bar-Yosef
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tal Tirosh-Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amir Vardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Mishali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gideon Paret
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yael Nevo-Caspi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yael Nevo-Caspi.

Ethics declarations

Ethics Approval and Consent to Participate

All procedures followed were in accordance with the ethical standards of the institutional and national committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. No animal studies were carried out by the authors for this article.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Associate Editor Marat Fudim oversaw the review of this article

Publisher’s Note

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

Supplementary Information

Figure S1

Association of clinical and postoperative parameters with the neurological status of the patients. Patients were divided in two groups: those that showed a neurological deficit upon discharge and those that did not. The following parameters were studied: A. Lactate levels six hours after the operation B. Time to discharge C. Time to initiation of oral nutrition D. Time to return to a baseline GCS score. Each box plot shows the 10th, 25th, 50th, 75th, and 90th percentile of the patients. ** p < 0.01 (PNG 340 kb)

High resolution image (TIF 17161 kb)

ESM 2

(DOCX 13.8 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zloto, K., Mor, L., Bar-Yosef, O. et al. MiRNA-124a: a Potential Biomarker for Neurological Deficits Following Cardiac Surgery in Pediatric Patients. J. of Cardiovasc. Trans. Res. 14, 1165–1172 (2021). https://doi.org/10.1007/s12265-021-10127-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-021-10127-7

Keywords

Search

Navigation