Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity.
OBJECTIVE
To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population.


METHODS
Prospective survey.


METHODS
Pediatric intensive care unit in a university-based children's hospital.


METHODS
Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale < 8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care.


METHODS
None.


RESULTS
Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale < or = 4 vs. > 4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (< or = 4 vs. > 4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury.


CONCLUSIONS
Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.
Robertson
C L
CL
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Bell
M J
MJ
Kochanek
P M
PM
Adelson
P D
PD
Ruppel
R A
RA
Carcillo
J A
JA
Wisniewski
S R
SR
Mi
Z
Z
Janesko
K L
KL
Clark
R S
RS
Marion
D W
DW
Graham
S H
SH
Jackson
E K
EK
D000241:Adenosine / Q000134:cerebrospinal fluid*; D000293:Adolescent; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D002649:Child Abuse; D002675:Child, Preschool; D018846:Excitatory Amino Acids / Q000134:cerebrospinal fluid; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D007223:Infant; D016014:Linear Models; D015999:Multivariate Analysis; D010414:Pennsylvania; D011446:Prospective Studies; D013997:Time Factors
D018846:Excitatory Amino Acids; D018698:Glutamic Acid; D000241:Adenosine