• William M Armstead and Ramesh Raghupathi.
• Department of Anesthesiology and Critical Care and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA. armsteaw@uphs.upenn.edu
• Neurol. Res. 2011 Mar 1; 33 (2): 127-32.

ObjectiveThis study characterized the association between endothelin-1, cerebral hemodynamics, and histopathology after fluid percussion brain injury in the newborn pig.MethodsLateral fluid percussion injury was induced in newborn pigs equipped with a closed cranial window. Cerebral blood flow was determined with radiolabeled microspheres and cerebrospinal fluid endothelin-1 was measured by radioimmunoassay.ResultsCerebrospinal fluid endothelin-1 was increased from 26±4 to 296±37 pg/ml (∼10(-10) M) at 8 hours following fluid percussion injury. Post-injury treatment (30 minutes) with the endothelin-1 antagonist BQ-123 (1 mg/kg, intravenous) blocked pial artery vasoconstriction to topical endothelin-1 (∼10(-10) M) and blunted fluid percussion injury-induced reductions in cerebral blood flow at 8 hours post-insult (56±6 and 26±4 ml/minute versus 57±6 and 40± ml/minute; 100 g for cerebral blood flow before injury and 8 hours post-fluid percussion injury in vehicle and BQ-123 post-treated animals, respectively). Fluid percussion injury resulted in neuronal cell loss and decreased microtubule associated protein 2 immunoreactivity in the parietal cortex, which were blunted by BQ-123.DiscussionThese data indicate that fluid percussion injury-induced changes in cerebral hemodynamics are associated with neuronal damage and that endothelin-1 contributes to fluid percussion injury-induced histopathologic changes.

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