Skip to main content


Log in

Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients

  • Original work
  • Published:
Neurocritical Care Aims and scope Submit manuscript



The objectives of this study were to assess the association between serum caspase 1 levels and known clinical and radiological prognostic factors and determine whether caspase 1was a more powerful predictor of outcome after traumatic brain injury (TBI) than clinical indices alone, to determine the association between the serum levels of caspase 1 and the 6-month outcome, and to evaluate if there is any association between caspase 1 with clinical and radiological variables.


This prospective and observational study was conducted in a university hospital and included patients with TBI who required hospital admission. Serum samples were collected at hospital admission and 24 h after TBI. Caspase 1 levels were determined by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were obtained to test the potential of caspase 1 to predict mortality (Glasgow Outcome Scale Extended score of 1) and unfavorable outcome (Glasgow Outcome Scale Extended scores of 1–4). Multivariate logistic regression was used to assess the effect of serum caspase 1 levels, adjusted by known clinical and radiological prognostic indices, on the outcome.


One hundred thirty-two patients and 33 healthy controls were included. We obtained 6-month outcome in 118 patients. On admission, the mean serum levels of caspase 1 were higher in patients with TBI compared with controls (157.9 vs. 108.5 pg/mL; p < 0.05) but not at 24 h after TBI. Serum caspase 1 levels on admission were higher in patients with unfavorable outcomes (189.5 vs. 144.1 pg/mL; p = 0.009). Similarly, serum caspase 1 levels on admission were higher in patients who died vs. patients who survived (213.6 vs. 146.8 pg/mL; p = 0.03). A logistic regression model showed that the serum caspase 1 level on admission was an independent predictor of 6-month unfavorable outcomes (odds ratio 1.05; 95% confidence interval 1–1.11; p = 0.05). Caspase 1 levels were higher in patients with severe TBI compared with those with moderate TBI, those with mild TBI, and healthy controls (p < 0.001). We did not find any correlation between caspase 1 and the radiological variables studied.


In this cohort of patients with TBI, we show that serum caspase 1 protein levels on admission are an independent prognostic factor after TBI. Serum caspase 1 levels on admission are higher in patients who will present unfavorable outcomes 6 months after TBI. Caspase 1 levels on admission are associated with the injury severity determined by the Glasgow Coma Scale.

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

Access this article

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  1. Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, et al. InTBIR participants and investigators traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987–1048.

    Article  Google Scholar 

  2. de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci. 2008;28(13):3404–14.

    Article  Google Scholar 

  3. Kigerl KA, de Rivero Vaccari JP, Dietrich WD, Popovich PG, Keane RW. Pattern recognition receptors and central nervous system repair. Exp Neurol. 2014;258:5–16.

    Article  CAS  Google Scholar 

  4. de Rivero Vaccari JP, Lotocki G, Alonso OF, Bramlett HM, Dietrich WD, Keane RW. Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J Cereb Blood Flow Metab. 2009;29(7):1251–61.

    Article  Google Scholar 

  5. de Rivero Vaccari JP, Dietrich WD, Keane RW. Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J Cereb Blood Flow Metab. 2014;34(3):369–75.

    Article  Google Scholar 

  6. Adamczak S, Dale G, de Rivero Vaccari JP, Bullock MR, Dietrich WD, Keane RW. Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article. J Neurosurg. 2012;117(6):1119–25.

    Article  CAS  Google Scholar 

  7. Kerr N, Lee SW, Perez-Barcena J, Crespi C, Ibañez J, Bullock MR, et al. Inflammasome proteins as biomarkers of traumatic brain injury. PLoS ONE. 2018;13(12):e0210128.

    Article  Google Scholar 

  8. Perez-Barcena J, Crespi C, Frontera G, Llompart-Pou JA, Salazar O, Goliney V, et al. Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome. J Neurosurg. 2020:1–6.

  9. Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, et al. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med. 2008;5(8):e165.

    Article  Google Scholar 

  10. Marshall LF, Marshall SB, Klauber MR, Van Berkum CM, Eisenberg H, Jane JA, et al. The diagnosis of head injury requires a classification based on computed axial tomography. J Neurotrauma. 1992;9(Suppl 1):S287-292.

    PubMed  Google Scholar 

  11. Raj R, Siironen J, Skrifvars MB, Hernesniemi J, Kivisaari R. Predicting outcome in traumatic brain injury: development of a novel computerized tomography classification system (Helsinki computerized tomography score). Neurosurgery. 2014;75(6):632–46.

    Article  Google Scholar 

  12. Yao S, Song J, Shun L, Cao C, Fang L, Wang C, et al. Helsinki computed tomography scoring system can independently predict long term outcome in traumatic brain injury. World Neurosurg. 2017;101:528–33.

    Article  Google Scholar 

  13. Kerr N, Garcia-Contreras M, Abbassi S, Mejias NH, Desousa BR, Ricordi C, et al. Inflammasome proteins in serum and serum-derived extracellular vesicles as biomarkers of stroke. Front Mol Neurosci. 2018;11:309.

    Article  Google Scholar 

  14. Keane RW, Dietrich WD, de Rivero Vaccari JP. Inflammasome proteins as biomarkers of multiple sclerosis. Front Neurol. 2018;9:135.

    Article  Google Scholar 

  15. Scott XO, Stephens ME, Desir MC, Dietrich WD, Keane RW, de Rivero Vaccari JP. The inflammasome adaptor protein ASC in mild cognitive impairment and Alzheimer’s disease. Int J Mol Sci. 2020;21(13):4674.

    Article  CAS  Google Scholar 

  16. Syed SA, Beurel E, Loewenstein DA, Lowell JA, Craighead WE, Dunlop BW, et al. Defective inflammatory pathways in never-treated depressed patients are associated with poor treatment response. Neuron. 2018;99(5):914-24.e3.

    Article  CAS  Google Scholar 

  17. de Rivero Vaccari JP, Dietrich WD, Keane RW. Therapeutics targeting the inflammasome after central nervous system injury. Transl Res. 2016;167(1):35–45.

    Article  Google Scholar 

  18. Abulafia DP, de Rivero Vaccari JP, Lozano JD, Lotocki G, Keane RW, Dietrich WD. Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J Cereb Blood Flow Metab. 2009;29(3):534–44.

    Article  CAS  Google Scholar 

  19. Kerr N, de Rivero Vaccari JP, Dietrich WD, Keane RW. Neural-respiratory inflammasome axis in traumatic brain injury. Exp Neurol. 2020;323:113080.

    Article  CAS  Google Scholar 

  20. Lee SW, de Rivero Vaccari JP, Truettner JS, Dietrich WD, Keane RW. The role of microglial inflammasome activation in pyroptotic cell death following penetrating traumatic brain injury. J Neuroinflammation. 2019;16(1):27.

    Article  Google Scholar 

  21. Desu HL, Plastini M, Illiano P, Bramlett HM, Dietrich WD, de Rivero Vaccari JP, et al. IC100: a novel anti-ASC monoclonal antibody improves functional outcomes in an animal model of multiple sclerosis. J Neuroinflammation. 2020;17(1):143.

    Article  CAS  Google Scholar 

  22. Kawata K, Tierney R, Langford D. Blood and cerebrospinal fluid biomarkers. Handb Clin Neurol. 2018;158:217–33.

    Article  Google Scholar 

  23. Kerr NA, de Rivero Vaccari JP, Abbassi S, Kaur H, Zambrano R, Wu S, et al. Traumatic brain injury-induced acute lung injury: evidence for activation and inhibition of a neural-respiratory-inflammasome axis. J Neurotrauma. 2018;35(17):2067–76.

    Article  Google Scholar 

  24. Agoston DV, Shutes-David A, Peskind ER. Biofluid biomarkers of traumatic brain injury. Brain Inj. 2017;31(9):1195–203.

    Article  Google Scholar 

Download references


This work was supported by a public grant from the Fondo de Investigación Sanitaria to Dr Jon Pérez-Bárcena (FIS-PI16/00737).

Author information

Authors and Affiliations



Jon Pérez-Bárcena wrote the first draft, conceptualization, data collection, data analysis, funding, wrote the submitted version. Javier Rodríguez Pilar collected data, performed the 6-month GOSE evaluations and critical review, and gave final approval. Osman Salazar performed the initial and 24-h CT scans analysis and critical review and gave final approval. Catalina Crespí performed laboratory experiments and critical review and gave final approval. Guillem Frontera performed the statistical analysis and critical review and gave final approval. Mariana Andrea Novo performed data collection and critical review and gave final approval. María Begoña Guardiola performed data collection and critical review and gave final approval. Juan Antonio Llompart-Pou performed data collection and critical review and gave final approval. Javier Ibáñez performed conceptualization and critical review and gave final approval. Juan Pablo de Rivero Vaccari performed conceptualization and critical review and gave final approval.

Corresponding author

Correspondence to Jon Pérez-Bárcena.

Ethics declarations

Conflicts of interest

JPdRV is a co-founder and managing members of InflamaCORE, LLC and have licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. JPdRV is Scientific Advisory Board Members of ZyVersa Therapeutics. No financial disclosure is reported for the rest of the authors.

Ethical approval/informed consent

The authors confirm compliance with ethical approval and informed consent for human studies.

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

Pérez-Bárcena, J., Rodríguez Pilar, J., Salazar, O. et al. Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients. Neurocrit Care 36, 527–535 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: