Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis

Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS dam age during neonatal meningitis. We tested (i) the hypothesis that cerebrova scular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive m ediators such as prostaglandins and (or) nitric oxide (NO), and (iii) wheth er this impairment is preventable by specific and (or) nonspecific inhibito rs: dexamethasone, ibuprofen, and N omega-nitro-L-arginine, a NO inhibitor. Sterile saline or 10(9) colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets. CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon- tipped catheters placed in the aorta. GBS produced a narrow range of CBF au toregulation due to an impairment at the upper limit of CPP. We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GB S impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen , dexamethasone, and N omega-nitro-L-arginine not only prevent this GBS-ind uced autoregulatory impairment but improve the range of cerebrovascular aut oregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the indu ction of NO synthase gene expression. Thus, acute early onset GBS-induced i mpairment of the upper limit of CBF autoregulation can be correlated with i ncreases of NO synthase production, suggesting that NO is a vasoactive medi ator of CBF.