endothelin-1 and Meningitis--Aseptic

Neurogenic pulmonary edema (NPE) is a fatal complication in children with enterovirus 71 (EV71) encephalitis. Endothelin 1 (ET-1), a potent vasoconstrictor, can induce pulmonary edema in rats via intrathecal injections. Thus, it was hypothesized that ET-1 in the central nervous system may correlate with NPE in children with EV71 encephalitis.. Clinical data and ET-1 in the cerebrospinal fluid (CSF) were compared between three groups: (1) EV71 encephalitis with NPE; (2) EV71 encephalitis without NPE; and (3) non-EV71 aseptic meningitis. ET-1 immunostaining was performed on the brainstem of autopsy patients.. The EV71 with NPE group showed significantly increased CSF levels of ET-1 compared to the EV71 without NPE and the non-EV71 aseptic meningitis groups (both p<0.01). The optimum cut-off point of ET-1 to predict NPE in EV71 patients, based on the receiver operating characteristic curve, was 0.5 pg/ml (sensitivity 83%, specificity 100%). Immunostaining in the brainstem showed increased ET-1 expression, mainly in the oligodendrocytes, in EV71 with NPE patients compared with control patients.. ET-1 in the central nervous system may play a role in the development of NPE in children with EV71 infection and could be used as a biomarker or therapeutic target for NPE in EV71 encephalitis.

Topics: Animals; Brain Stem; Child, Preschool; Encephalitis, Viral; Endothelin-1; Enterovirus A, Human; Enterovirus Infections; Female; Humans; Infant; Male; Meningitis, Aseptic; Pulmonary Edema; Rats

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between

Topics: Animals; Animals, Newborn; Blood Pressure; Brain Chemistry; Cerebrospinal Fluid Proteins; Cerebrovascular Circulation; Endothelin-1; Endothelins; Hypertension; Hypotension; Leukocyte Count; Meningitis, Aseptic; Protein Precursors; Streptococcus agalactiae; Swine; Vascular Resistance