NSE and S100 after Hypoxia in the Newborn Pig

Abstract

Perinatal asphyxia is an important cause of neonatal morbidity and mortality. There is the potential to halt cerebral damage if neural rescue strategies are applied within a short period of time after an insult. It is therefore important to be able to accurately identify neonates who may benefit from neural rescue therapies. Recent studies in asphyxiated neonates have correlated S100B and NSE with outcome; however, interpretation of these studies were difficult, as the timing of the measurements were not consistent. We measured NSE and S100 in 1-d-old piglets after a mild or severe hypoxic insult. Measurements were performed at 6 -72 h after the insult and correlated with histologic outcome. There were no differences of the NSE or S100 concentrations between controls and the mild hypoxia group. After 24 h, there was a significant difference of NSE between the control/mild insult group and severe insult group. After 48 h, the S100 concentrations were significantly different between the control/ mild insult group and the severe insult group. Both proteins showed good correlation at these time points with outcome as measured by histology score at 72 h. In conclusion, NSE and S100B measured in the serum of piglets after hypoxia increased significantly and correlated with outcome. This increase occurs too late to be used within the first 24 h but might be helpful for the clinician in determining the timing of an insult. Perinatal asphyxia occurs in 1 in 500 deliveries and is an important cause of neonatal morbidity and mortality. There is the potential of neural rescue therapies to halt cerebral damage when applied within a "window of opportunity" of limited duration. It is therefore especially important to be able to accurately identify those neonates who may benefit from such interventions (1). The early and accurate prediction of the severity of brain damage remains difficult. Several brain-specific proteins have been measured in CSF and serum and correlated with outcome after hypoxic/ischemic reperfusion injury (1-4). S100 is an astroglial specific protein with calcium binding capacity. It is a homo-or heterodimer consisting of two subunits, alpha and beta. S100␤␤ is present in high concentrations in glial and Schwann cells, S100␣␣ in glial cells, and S100␣␤ in striated muscle, heart, and kidney (5). NSE is an isoenzyme of the glycolytic enzyme enolase and is present in high concentrations in neuronal cell bodies, axons, and in cells of neuroendocrine origin (6). After neuronal injury, S100B (S100␤␤) and NSE pass into the CSF and across the blood-brain-barrier (6,7). Recent studies in asphyxiated neonates have correlated S100B and NSE with outcome (3,4,8,9). The results correlated with outcome but measurements had been taken at differing and unknown times after insult and from different bodily fluids (serum or CSF). As the probable beginning and duration of the insult in neonates is often uncertain, correlations with outcome are difficult to interpret as the timeline of the increase of NSE or S100 after an insult...

Effects of dexmedetomidine on the expression of inflammatory factors in children with congenital heart disease undergoing intraoperative cardiopulmonary bypass: a randomized controlled trial

“…Therefore, we evaluated both TNF‐α and IL‐6 in the inflammatory response of the brain in this study. Because the half‐lives of S‐100β protein and NSE are different, we measured both of them in the present study to monitor the dynamic changes in brain damage 18‐21 …”

“…Because the half-lives of S-100β protein and NSE are different, we measured both of them in the present study to monitor the dynamic changes in brain damage. [18][19][20][21] Dexmedetomidine is a highly selective central α 2 -AR agonist. In addition to its sedative, analgesic, and anxiolytic effects, dexmedetomidine also protects brain tissue and has a significant neuroprotective effect.…”

Application of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method to identify potential biomarkers of perinatal asphyxia in a non-human primate model

“…Identification of these altered metabolites, or biomarkers, might provide sensitive and specific information about severity of injury. Some potential markers such as neuron-specific enolase [13] and S100 [14,15] have been previously identified and are being investigated further, but it is important to continue searching for markers that can predict the timing and severity of the perinatal event and its neurologic outcome.…”

Kinetics of serum S100B in newborns with intracranial lesions

“…They also argued that given a post‐partum increase in S100 with a reported half‐life ≤2 h in HIE newborns with brain disorders, the increased serum S100 level in HIE newborns could not be accounted for only from the S100 produced in the umbilical cord and placenta. Kecskes et al measured blood serum S100B at regular intervals in newborn piglets and reported that serum S100 protein levels in newborns at 48 and 72 h after birth were significantly higher in the severe HIE group than in the normal and lower HIE group 14 . They also noted a good correlation between serum S100B level and histopathological brain findings at 72 h after birth.…”