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Endothelin inhibition improves cerebral blood flow and is neuroprotective in pneumococcal meningitis
Author(s) -
Pfister Luz Andrea,
Tureen Jay H.,
Shaw Sydney,
Christen Stephan,
Ferriero Donna M.,
Täuber Martin G.,
Leib Stephen L.
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200003)47:3<329::aid-ana8>3.0.co;2-r
Subject(s) - medicine , endothelin receptor , endothelins , bosentan , meningitis , cerebrospinal fluid , cerebral blood flow , anesthesia , endothelin receptor antagonist , endothelin 1 , ceftriaxone , surgery , biology , antibiotics , microbiology and biotechnology , receptor
By using an infant rat model of pneumococcal meningitis, we determined whether endothelins contribute to neuronal damage in this disease. Cerebrospinal fluid analysis demonstrated a significant increase of endothelin‐1 in infected animals compared with uninfected controls. Histopathological examination 24 hours after infection showed brain damage in animals treated with ceftriaxone alone (median, 9.2% of cortex; range, 0–49.1%). In infected animals treated intraperitoneally with the endothelin antagonist bosentan (30 mg/kg, every 12 hours) also, injury was reduced to 0.5% (range, 0–8.6%) of cortex. Cerebral blood flow was reduced in infected animals (6.5 ± 4.0 ml/min/100 g of brain vs 14.9 ± 9.1 ml/min/100 g in controls. Treatment with bosentan restored cerebral blood flow to levels similar to controls (12.8 ± 5.3 ml/min/100 g). Improved blood flow was not mediated by nitric oxide production, because bosentan had no effect on cerebrospinal fluid or plasma nitrite/nitrate concentrations at 6, 12, or 18 hours. These data indicate that endothelins contribute to neuronal injury in this model of pneumococcal meningitis by causing cerebral ischemia. Ann Neurol 2000;47:329–335