Serum substance P levels are associated with severity and mortality in patients with severe traumatic brain injury

Abstract

IntroductionSubstance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes. SP is released early following acute injury to the CNS, promoting a neurogenic inflammatory response characterized by an increase in the permeability of the blood–brain barrier and the development of vasogenic edema. High levels of SP could lead to an exacerbated inflammatory response that could be fatal for patients with traumatic brain injury (TBI). Thus, the main goal of the present study was to determine whether serum SP levels are associated with injury severity and mortality in patients with severe TBI.MethodsThis multicenter, observational, prospective study was carried out in six Spanish intensive care units and included patients with Glasgow Coma Scale (GCS) scores ≤8. Patients with an Injury Severity Score ≥10 in non-cranial aspects were excluded. Blood samples were collected on day 1 of TBI to measure serum SP levels. The endpoint was 30-day mortality.ResultsWe found higher serum SP levels (P =0.002) in non-surviving patients (n =27) than in surviving patients (n =73). The area under the curve for serum SP levels with regard to predicting 30-day mortality was 0.70 (95% confidence interval (CI), 0.60 to 0.79; P <0.001). Survival analysis showed that patients with serum SP levels >299 pg/ml had higher 30-day mortality than patients with lower levels (hazard ratio =3.7; 95% CI, 1.75 to 7.94; P <0.001). Multiple binomial logistic regression analysis showed that serum SP levels >299 pg/ml were associated with 30-day mortality when we controlled for APACHE II score and Marshall computed tomography lesion classification (odds ratio (OR) =5.97; 95% CI, 1.432 to 24.851; P =0.01) and for GCS score and age (OR =5.71; 95% CI, 1.461 to 22.280; P =0.01). We found a negative association between serum SP levels and GCS score (Spearman’s ρ = −0.22; P =0.03).ConclusionsWe report, for the first time to our knowledge, that serum SP levels were associated with injury severity and mortality in patients with severe TBI. These results open the possibility that SP antagonists may be useful in the treatment of patients with severe TBI.

New Prognostic Biomarkers in Patients With Traumatic Brain Injury

“…In a study by our team (to our knowledge, the first study to include data on serum SP levels in patients with severe TBI) was found that non surviving TBI patients showed higher serum SP levels than survivors (420 (310 - 815) vs. 250 (99 - 496); P = 0.002), and that serum SP levels were associated with TBI severity and with early mortality ( 24 ). We found that the area under the curve (AUC) for serum SP levels as a predictor of 30-day mortality was 0.70 (95% CI = 0.60-0.79; P < 0.001).…”

Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides

“…Substances P plays role in inflammation through astrocyte and leukocyte activation at the site of injury (Lorente et al, 2015). A number of enzymes are required in the metabolism of substances P, including: neutral endopeptidase (NEP), angiotensin-converting enzyme (ACE), substance-P-degrading enzyme, cathepsin-D and cathepsin-E.…”

Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury

“…High SP levels in the serum of patients with severe TBI have reportedly correlated with increased mortality (Lorente et al, 2015). Elevated SP serum levels have also been reported in patients with major depression, levels that decline in responders treated with antidepressant (Bondy et al, 2003).…”