Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome

J Neurosurg. 2020 May 1;134(5):1644-1649. doi: 10.3171/2020.2.JNS193079. Print 2021 May 1.

Abstract

Objective: The objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury.

Methods: This is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale-Extended.

Results: A total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI.

Conclusions: In this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.

Keywords: inflammasome; inflammation; innate immunity; intracranial pressure; traumatic brain injury.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Brain Injuries, Traumatic / blood
  • Brain Injuries, Traumatic / cerebrospinal fluid*
  • Brain Injuries, Traumatic / enzymology
  • Brain Injuries, Traumatic / surgery
  • Caspase 1 / cerebrospinal fluid*
  • Cerebral Ventricles
  • Drainage
  • Female
  • Humans
  • Immunity, Innate
  • Inflammasomes
  • Intracranial Hypertension / etiology*
  • Intracranial Hypotension / etiology*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / cerebrospinal fluid*
  • Prospective Studies
  • Treatment Outcome
  • Ventriculostomy
  • Young Adult

Substances

  • Inflammasomes
  • Nerve Tissue Proteins
  • Caspase 1