Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in infants and children

Adrenomedullin is a recently discovered 52-amino acid peptide that is a pot ent vasodilator and is produced in the brain in experimental models of cere bral ischemia. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats, and thus may represent an endogenous neuroprotectant. Disturbances in cerebral bloo d flow (CBF), including hypoperfusion and hyperemia, frequently occur after severe traumatic brain injury (TBI) in infants and children. We hypothesiz ed that cerebrospinal fluid (CSF) adrenomedullin concentration would be inc reased after severe TBI in infants and children, and that increases in adre nomedullin would be associated with alterations in CBF. We also investigate d whether posttraumatic CSF adrenomedullin concentration was associated wit h relevant clinical variables (CBF, age, Glasgow Coma Scale [GCS] score, me chanism of injury, and outcome). Total adrenomedullin concentration was mea sured using a radioimmunometric assay. Sixty-six samples of ventricular CSF from 21 pediatric patients were collected during the first 10 days after s evere TBI (GCS score < 8). Control CSF was obtained from children (n = 10) undergoing lumbar puncture without TBI or meningitis. Patients received sta ndard neurointensive care, including CSF drainage. CBF was measured using X enon computed tomography (CT) in 11 of 21 patients. Adrenomedullin concentr ation was markedly increased in CSF of infants and children after severe TB I vs control (median 4.5 versus 1.0 fmol/mL, p < 0.05). Sixty-two of 66 CSF samples (93.9%) from head-injured infants and children had a total adrenom edullin concentration that was greater than the median value for controls. Increases in CSF adrenomedullin were most commonly observed early after TBI . CBF was positively correlated with CSF adrenomedullin concentration (p < 0.001), but this relationship was not significant when controlling for the effect of time. CSF adrenomedullin was not significantly associated with ot her selected clinical variables. We conclude adrenomedullin is markedly inc reased in the CSF of infants and children early after severe TBI. We specul ate that adrenomedullin participates in the regulation of CBF after severe TBI.