Table 1.
Inflammatory mediator | Tissue / Fluid | Time Course | Association with clinical outcome(s) | Other | Ref |
---|---|---|---|---|---|
Triggers / Brakes | |||||
Adenosine | CSF ECF |
Increased within hours of injury Rapidly decline over 12–24h |
Pediatric: No association with outcome after severe TBI Adult: Higher level in patients that died after severe TBI |
A1AR gene variants associated with post-traumatic epilepsy Increased CSF adenosine associated with jugular vein desaturation |
222–224 |
Complement | CSF | Peak day 1 post-injury, decline day 2–7 | Adult: Increased MAC level associated with BBB dysfunction in severe TBI | C3 and Factor B increased relative to controls | 58,225 |
Tissue | Increased in tissue resected 2–82h post-injury | Unknown | C3-mRNA also detected in penumbra, suggesting a contribution of local synthesis | 57 | |
Glutamate | CSF ECF |
Multiple courses described Most common peak day 1, decline day 2–3 |
Pediatric: Higher level associated with poor 6mo-GOS in severe TBI Adult: Increase in ECF glutamate associated with poor outcomes |
Increased glutamate associated with age < 4 and child abuse Hourly levels not affected by transient hemodynamic or ICP change |
41,226–228 |
HMGB1 | CSF | No change over time | Pediatric: Higher level associated with unfavorable 6 month GOS in severe TBI Adults: Increased level associated with high ICP |
Not associated with age or mechanism of injury | 27,28 |
Tissue | Translocated to cytoplasm of cells in contused area at 30min – 1d Localized to cytoplasm of phagocytic microglia at 2–20d |
Unknown | HMGB1 receptor, RAGE, expression also increased in contused area in phagocytic microglia | 229 | |
NLRP1 | CSF | Unknown | Adult: Higher level in patients with unfavorable 5 month GOS in moderate to severe TBI | Adaptor protein ASC also increased in CSF of TBI patients | 230 |
Caspase-1 | CSF | Unknown | Adult: Higher level in patients with unfavorable 5mo-GOS in moderate to severe TBI | Identified by p20 subunit suggests activated form of enzyme | 230 |
Tissue | Pro-caspase-1 is cleaved to active form on day 1 | Unknown | 231 | ||
mtDNA | CSF | Peak day 1, declined on day 3, though still above control | Pediatric: Higher levels associated with unfavorable 6mo- GOS in severe TBI | Positively correlated with HMGB1 level | 52 |
Abbreviations: TBI – traumatic brain injury; CSF – Cerebrospinal fluid; ECF – Extracellular fluid; A1AR – adenosine receptor A1; MAC – membrane attack complex; ICP – intracranial pressure; HMGB1 – high mobility group box 1; RAGE – receptor for advanced glycation endproducts; NLRP1 – NACHT, LRR and PYD domains-containing protein 1; GOS – Glasgow Outcome Scale; mtDNA – mitochondria DNA; BBB – blood brain barrier; GCS – Glasgow Coma Scale