Increased adenosine concentration in cerebrospinal fluid after severe traumatic brain injury in infants and children: Association with severity of injury

Introduction: Traumatic brain injury (TBI) in children results in a myriad of pathophysiologic derangements that contribute to secondary injury, including hypoperfusion, energy failure and excitotoxicity. In addition, a number of endogenous neuroprotectants are produced after TBI, including adenosine, which increases cerebral blood flow and reduces metobolic demands^1,2. In a prior evaluation of cerebrospinal fluid (CSF) of children following severe TBI³, we demonstrated increased peak levels of adenosine after TBI. In the current study, we evaluate the CSF of an expanded sample of infants and children following severe TBI, and examine the contribution of age, GCS, mechanism of injury and time after injury to CSF adenosine levels. Methods: Samples (n=304) of ventricular CSF were collected from 27 infants and children (2 mo to 14 y) during the first 7 d after severe TBI (GCS <8). Control CSF samples (n=21) were obtained from infants and children without TBI or meningitis. Adenosine was measured using HPLC. Results: Mean adenosine level was markedly increased in CSF of children following TBI vs control (peak 33.5 ± 9.5 and mean 24.3 ± 9.5 vs control mean 3.8 ± 0.5 nmol/L, p<0.001). Using a multiple regression model, the increase in CSF adenosine was independently associated with GCS ≤4 vs >4 and time after injury (both p<0.05). However, increased adenosine was not independently associated with mechanism of injury (abuse vs other) or age (≤4 vs > 4y). Conclusions: We conclude CSF adenosine concentration is increased in infants and children after severe TBI. This increase was especially pronounced in children with the most severe injuries. Unlike mediators of secondary damage, such as glutamate ⁴, adenosine was not associated with child abuse or age ≤4 y. We speculate that adenosine may play an important role in endogenous attempts at neuroprotection after TBI.