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Acute phase response after fatal traumatic brain injury

Abstract

An inflammatory response occurring after fatal traumatic brain injury (TBI) initiates time-dependent cascades of acute phase response. This may offer the potential to monitor postmortem biomarker levels of several pro-inflammatory cytokines to gain information about the cause of death and the trauma survival time. Cerebrospinal fluid (CSF) and serum samples were collected from forensic autopsies of 95 adult cadavers after postmortem intervals up to 6 days. The cases were divided according to their cause of death into fatal TBI (n = 46) with different survival times and age- and gender-matching non-TBI fatalities as controls (n = 49). Quantitative marker levels of interleukin-6 (IL-6), ferritin, soluble tumor necrosis factor receptor type 1, C-reactive protein, and lactate dehydrogenase were analyzed using immunoassays. Standardized statistical tests were performed to differentiate causes of death and survival time of TBI cases. The CSF IL-6, ferritin, and LDH levels after TBI were significantly higher than those in the controls (p < 0.001). Only serum IL-6 values showed comparable differences (p < 0.05). Both CSF and serum ferritin levels were discriminative between early and delayed death after TBI (p < 0.05). There were partly distinctive correlations between marker levels in both fluids with rising values after longer survival. There were up to moderate correlation between the marker levels and the postmortem interval due to postmortem hemolysis. However, neither CSF nor serum level ranges were affected by the age or gender of the subjects. This study is the first to measure all five proteins systematically in postmortem trauma cases. Ferritin and IL-6 proved themselves to be interesting postmortem biomarkers to provide specific information on the injury pattern and the survival time of traumatic fatalities. Such forensic investigations could serve as inexpensive and fast laboratory tests.

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Acknowledgments

The authors would like to cordially thank Philip Saunders (Language Support Services; Berlin, Germany) for proofreading this paper as a native speaker.

Funding information

This work was partly supported by the German Ministry of Defense.

Author information

Correspondence to Benjamin Ondruschka.

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Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Table S1:

Clinical and pathological characteristics of the individuals died from traumatic brain injury. ISS, injury severity score; GCS, Glasgow coma scale; CPR, cardiopulmonary resuscitation; g; grams; h, hours; PMI, postmortem interval; TBI, traumatic brain injury; w, women; m, men; sec, seconds; min, minutes; d, days; n.d., no documentation. (XLSX 15 kb)

Table S2:

Clinical and pathological characteristics of the individuals served as control cases. ISS, injury severity score; CPR, cardiopulmonary resuscitation; g; grams; h, hours; PMI, postmortem interval; w, women; m, men; min, minutes. (XLSX 13 kb)

Table S3:

Results of rank correlation calculation between the five markers of acute phase response and the hemolytic index as well as the postmortem interval in cerebrospinal fluid (CSF) and serum. (XLS 32 kb)

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Ondruschka, B., Schuch, S., Pohlers, D. et al. Acute phase response after fatal traumatic brain injury. Int J Legal Med 132, 531–539 (2018). https://doi.org/10.1007/s00414-017-1768-2

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Keywords

  • Acute phase response
  • Cytokines
  • Fatal traumatic brain injury
  • Inflammation
  • Postmortem biochemistry