Serum S-100beta as a possible marker of blood-brain barrier disruption.

Two brain-specific proteins, S-100beta and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100beta levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100beta is a marker of blood-brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100beta increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100beta is an early marker of BBB opening that is not necessarily related to neuronal damage.

Do peritoneal catheters remove pro-inflammatory cytokines after cardiopulmonary bypass in neonates?

BACKGROUND: Cardiopulmonary bypass (CPB) in neonates induces a cytokine-mediated capillary leak syndrome that can cause organ dysfunction. Removing harmful cytokines after CPB may attenuate this response. This study measured the concentrations of serum and peritoneal fluid (PF) cytokines after CPB to determine if harmful cytokines can be removed with peritoneal catheters. METHODS: Neonates (n = 18) had cardiac surgery using CPB with circulatory arrest. Peritoneal catheters were placed at the end of surgery to drain excess fluid. Serum samples were obtained before and after CPB, and PF after CPB. Cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Tumor necrosis factor-alpha and interleukin-1beta (IL-1beta) were not detected in any serum or PF sample. Serum concentrations of IL-6, IL-8, and IL-10 increased significantly after CPB. PF concentrations of IL-6 and IL-8 exceeded serum concentrations, whereas IL-10 concentrations were higher in the serum. There was a significant negative correlation between serum and PF concentrations of IL-6 after CPB (r = -0.63; p<0.05). CONCLUSIONS: PF has very high concentrations of the proinflammatory cytokines, IL-6 and IL-8, after CPB but not the antiinflammatory cytokine IL-10. The PF may be a depot for the harmful inflammatory cytokines after CPB, and removing the PF could lower serum concentrations.

Neuroprotective, anesthetic, and cardiovascular effects of the NMDA antagonist, CNS 5161A, in isoflurane-anesthetized lambs.

BACKGROUND: N-methyl-d-aspartate (NMDA) receptor antagonists are neuroprotective in animal models of cerebral ischemia, but adverse cardiovascular and neurobehavioral effects have precluded their clinical use. The authors present the neuroprotective, anesthetic, and cardiovascular effects of a novel NMDA antagonist, CNS 5161A. METHODS: Lambs, 4.0-6.5 kg, were anesthetized with isoflurane, intubated, and ventilated and had thermodilution catheters placed in the pulmonary artery and 20-g catheters placed in the femoral artery. The minimum alveolar concentration (MAC) of isoflurane was determined using the "bracketing technique." CNS 5161A was given as a bolus and then as an infusion at three doses. Cardiovascular measurements were determined every 15 min. Other lambs (n = 25) were subjected to cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) for 120 min. Eighteen received CNS 5161A, and seven received saline vehicle. One hour after CPB, brains were perfusion-fixed and removed for in situ hybridization and immunohistochemistry analysis in half of the animals. The other half survived 48 h before their brains were examined for neuronal degeneration. RESULTS: Isoflurane at MAC significantly decreased blood pressure, heart rate, cardiac output, and systemic vascular resistance by 30-48% (n = 16; P < 0.05). CNS 5161A (n = 12) had no significant cardiovascular effects. All concentrations of CNS 5161A caused a significant reduction (21-29%) of the MAC of isoflurane (n = 12; P < 0.05). CNS 5161A, at serum concentrations greater than 25 ng/ml, completely inhibited c-fosmRNA and c-FOS protein expression in hippocampal neurons after 120 min of HCA, attenuated neuronal degeneration, and improved functional outcome by 47% (P < 0.05). CONCLUSIONS: CNS 5161A at neuroprotective concentrations before CPB-HCA significantly reduces the MAC of isoflurane without cardiovascular effects.