OBJECTIVE: To measure quinolinic acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF quinolinic acid concentrations to clinically important variables. DESIGN: A prospective, observational study. SETTING: The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university-based children's hospital. PATIENTS: Seventeen critically ill children following severe TBI (Glasgow Coma Scale score <8) whose care required the placement of an intraventricular catheter for continuous drainage of CSF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 mos to 16 yrs (mean 6.0 yrs). CSF was collected immediately on placement of the ventricular catheter and daily thereafter. Quinolinic acid concentration was measured by gas chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per patient). CSF quinolinic acid concentration progressively increased after injury (p = .034, multivariate analysis) and was increased in nonsurvivors vs. survivors (p = .002, multivariate analysis). CSF quinolinic acid concentration was not associated with age. Although overall CSF quinolinic acid concentration was not associated with shaken injury (p = .16, multivariate analysis), infants suffering with shaken infant syndrome had increased admission CSF quinolinic acid concentrations compared with children with accidental mechanisms of injury (p = .027, Mann-Whitney Rank Sum test). CONCLUSIONS: A large and progressive increase in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI in children. The increase is strongly associated with increased mortality. Increased CSF quinolinic acid concentration on admission in children with shaken infant syndrome could reflect a delay in presentation to medical attention or age-related differences in quinolinic acid production. These findings raise the possibility that quinolinic acid may play a role in secondary injury after TBI in children and suggest an interaction between inflammatory and excitotoxic mechanisms of injury following TBI.
OBJECTIVE: To measure quinolinic acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF quinolinic acid concentrations to clinically important variables. DESIGN: A prospective, observational study. SETTING: The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university-based children's hospital. PATIENTS: Seventeen critically ill children following severe TBI (Glasgow Coma Scale score <8) whose care required the placement of an intraventricular catheter for continuous drainage of CSF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:Patients ranged in age from 2 mos to 16 yrs (mean 6.0 yrs). CSF was collected immediately on placement of the ventricular catheter and daily thereafter. Quinolinic acid concentration was measured by gas chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per patient). CSF quinolinic acid concentration progressively increased after injury (p = .034, multivariate analysis) and was increased in nonsurvivors vs. survivors (p = .002, multivariate analysis). CSF quinolinic acid concentration was not associated with age. Although overall CSF quinolinic acid concentration was not associated with shaken injury (p = .16, multivariate analysis), infants suffering with shaken infant syndrome had increased admission CSF quinolinic acid concentrations compared with children with accidental mechanisms of injury (p = .027, Mann-Whitney Rank Sum test). CONCLUSIONS: A large and progressive increase in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI in children. The increase is strongly associated with increased mortality. Increased CSF quinolinic acid concentration on admission in children with shaken infant syndrome could reflect a delay in presentation to medical attention or age-related differences in quinolinic acid production. These findings raise the possibility that quinolinic acid may play a role in secondary injury after TBI in children and suggest an interaction between inflammatory and excitotoxic mechanisms of injury following TBI.
Authors: Rosanne Salonia; Philip E Empey; Samuel M Poloyac; Stephen R Wisniewski; Megan Klamerus; Haishin Ozawa; Amy K Wagner; Randall Ruppel; Michael J Bell; Keri Feldman; P David Adelson; Robert S B Clark; Patrick M Kochanek Journal: J Neurotrauma Date: 2010-09-17 Impact factor: 5.269
Authors: Wei-Min Gao; Mandeep S Chadha; Rachel P Berger; Gilbert S Omenn; David L Allen; Michael Pisano; P David Adelson; Robert S B Clark; Larry W Jenkins; Patrick M Kochanek Journal: J Neurotrauma Date: 2007-01 Impact factor: 5.269
Authors: Liane N Rotta; André P Schmidt; Tadeu Mello e Souza; Cristina W Nogueira; Karine B Souza; Ivan A Izquierdo; Marcos L S Perry; Diogo O Souza Journal: Neurochem Res Date: 2003-08 Impact factor: 3.996
Authors: Timothy B Meier; Jonathan Savitz; Rashmi Singh; T Kent Teague; Patrick S F Bellgowan Journal: J Neurotrauma Date: 2016-01-13 Impact factor: 5.269
Authors: Sheryl E Arambula; Erin L Reinl; Nagat El Demerdash; Margaret M McCarthy; Courtney L Robertson Journal: Exp Neurol Date: 2019-03-02 Impact factor: 5.330
Authors: Timothy B Meier; Lezlie España; Morgan E Nitta; T Kent Teague; Benjamin L Brett; Lindsay D Nelson; Michael A McCrea; Jonathan Savitz Journal: Brain Behav Immun Date: 2020-11-08 Impact factor: 7.217