S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass.

OBJECTIVE: The present study is to describe the clinical impact of S100 and S100ß for the evaluation of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass (CPB). METHODS: Quantitative results of S100 and S100ß reported in the literature of the year range 1990-2014 were collected, screened and analyzed. RESULTS: Cerebrospinal fluid and serum S100 levels showed a same trend reaching a peak at the end of CPB. The cerebrospinal fluid/serum S100 ratio decreased during CPB, reached a nadir at 6 h after CPB and then increased and kept high untill 24 h after CPB. Serum S100 at the end of CPB was much higher in infant than in adults, and in on-pump than in off-pump coronary artery bypass patients. ∆S100 increased with age and CPB time but lack of statistical significances. Patients receiving an aorta replacement had a much higher ∆S100 than those receiving a congenital heart defect repair. Serum S100ß reached a peak at the end of CPB, whereas cerebrospinal fluid S100 continued to increase and reached a peak at 6 h after CPB. The cerebrospinal fluid/serum S100ß ratio decreased during CPB, increased at the end of CPB, peaked 1 h after CPB, and then decreased abruptly. The increase of serum S100ß at the end of CPB was associated with type of operation, younger age, lower core temperature and cerebral damages. ∆S100ß displayed a decreasing trend with age, type of operation, shortening of CPB duration, increasing core temperature, lessening severity of cerebral damage and the application of intervenes. Linear correlation analysis revealed that serum S100ß concentration at the end of CPB correlated closely with CPB duration. CONCLUSION: S100 and S100ß in cerebrospinal fluid can be more accurate than in the serum for the evaluations of cerebral damage in cardiac surgery. However, cerebrospinal fluid biopsies are limited. But serum S100ß and ∆S100ß seem to be more sensitive than serum S100 and ∆S100. The cerebral damage in cardiac surgery might be associated with younger age, lower core temperature and longer CPB duration during the operation. Effective intervenes with modified CPB circuit filters or oxygenators and supplemented anesthetic agents or priming components may alleviate the cerebral damage.

Biomarkers of brain damage in preterm infants.

OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. MATERIALS AND METHODS: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. RESULTS: Activin A, S100B protein and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.

Attenuation of interleukin-1beta by pulsed electromagnetic fields after traumatic brain injury.

Traumatic Brain Injury (TBI) is a major cause of morbidity and mortality in civilian and military populations. Interleukin-1beta (IL-1ß) is a pro-inflammatory cytokine with a key role in the inflammatory response following TBI and studies indicate that attenuation of this cytokine improves behavioral outcomes. Pulsed electromagnetic fields (PEMF) can reduce inflammation after soft tissue injuries in animals and humans. Therefore, we explored whether PEMF signals could alter the course of IL-1ß production in rats subjected to closed-head contusive weight-drop injuries (Marmarou method) and penetrating needle-stick brain injuries. Protein levels, measured by the Biorad assay, were not altered by injuries or PEMF treatment. In addition, we verified that IL-1ß levels in cerebrospinal fluid (CSF) were proportional to injury severity in the contusion model. Results demonstrate that PEMF treatment attenuated IL-1ß levels up to 10-fold in CSF within 6h after contusive injury and also significantly suppressed IL-1ß within 17-24h after penetrating injury. In contrast, no differences in IL-1ß were seen between PEMF-treated and control groups in brain homogenates. To the authors' knowledge, this is the first report of the use of PEMF to modulate an inflammatory cytokine after TBI. These results warrant further studies to assess the effects of PEMF on other inflammatory markers and functional outcomes.

Therapeutic evaluation of etanercept in a model of traumatic brain injury.

Antagonism of tumor necrosis factor-alpha with etanercept has proved to be effective in the treatment of spinal cord injury and centrally endotoxin-induced brain injury. However, etanercept may offer promise as therapy for traumatic brain injury (TBI). In this study, anesthetized rats, immediately after the onset of TBI, were divided into two major groups and given the vehicle solution (1 mL/kg of body weight) or etanercept (5 mg/kg of body weight) intraperitoneally once per 12 h for consecutive 3 days. Etanercept caused attenuation of TBI-induced cerebral ischemia (e.g., increased cellular levels of glutamate and lactate-to-pyruvate ratio), damage (e.g., increased cellular levels of glycerol) and contusion and motor and cognitive function deficits. TBI-induced neuronal apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase αUTP nick-end labeling and neuronal-specific nuclear protein double-positive cells), glial apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase αUTP nick-end labeling and glial fibrillary acidic protein double-positive cells), astrocytic (e.g., increased numbers of glial fibrillary acidic protein positive cells) and microglial (e.g., increased numbers of ionized calcium-binding adapter molecule 1-positive cells) activation and activated inflammation (e.g., increased levels of tumor necrosis factor-alpha, interleukin-1ß and interleukin-6) were all significantly reduced by etanercept treatment. These findings suggest that etanercept may improve outcomes of TBI by penetrating into the cerebrospinal fluid in rats.

Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury.

Hypocretin-1 is involved in the regulation of the sleep-wake cycle. The authors prospectively assessed CSF hypocretin-1 levels in 44 consecutive patients with acute traumatic brain injury (TBI). Compared with controls, hypocretin-1 levels were abnormally lower in 95% of patients with moderate to severe TBI and in 97% of patients with posttraumatic brain CT changes. Hypocretin-1 deficiency after TBI may reflect hypothalamic damage and be linked with the frequent development of posttraumatic sleep-wake disorders.

Effects of dopamine on posttraumatic cerebral blood flow, brain edema, and cerebrospinal fluid glutamate and hypoxanthine concentrations.

OBJECTIVES: Dopamine is often used in the treatment of traumatic brain injury to maintain cerebral perfusion pressure. However, it remains unclear whether dopamine contributes to secondary brain injury caused by vasoconstriction and resulting diminished cerebral perfusion. The present study investigated the effects of dopamine in different concentrations on posttraumatic cortical cerebral blood flow (CBF), brain edema formation, and cerebrospinal fluid concentrations of glutamate and hypoxanthine. DESIGN: Randomized, placebo-controlled trial. SETTING: Animal laboratory. SUBJECTS: Eighteen male Sprague-Dawley rats subjected to a focal cortical brain injury. INTERVENTIONS: Four hours after controlled cortical impact, rats were randomized to receive physiologic saline solution (n = 6), 10-12 tig/kg/min dopamine (n = 6), or 40-50 microg/kg/min dopamine (n = 6), for 3 hrs. Cortical CBF was measured over both hemispheres by using laser-Doppler flowmetry before trauma and before, during, and after the infusion period. At 8 hrs after trauma, brains were removed to determine hemispheric swelling and water content. Cisternal cerebrospinal fluid was sampled to measure glutamate and hypoxanthine. MEASUREMENTS AND MAIN RESULTS: After trauma, cortical CBF was significantly decreased by 46% within the vicinity of the cortical contusion in all rats. Infusion of saline and 10-12 ig/kg/min dopamine did not change mean arterial blood pressure (MABP) or cortical CBF. However, infusion of 40-50 microg/kg/min dopamine, which elevated MABP from 89 to 120 mm Hg, significantly increased posttraumatic CBF within and around the contusion by 35%. Over the nontraumatized hemisphere, CBF remained unchanged. Hemispheric swelling, water content, cerebrospinal fluid glutamate, and hypoxanthine levels were not affected by dopamine in the given dosages. CONCLUSIONS: Under the present study design, there was no evidence for a dopamine-mediated vasoconstriction, because posttraumatic cortical CBF was increased by dopamine-induced elevation of MABP. However, the increase in CBF did not significantly affect edema formation or cerebrospinal fluid glutamate and hypoxanthine levels.

[The effect of the different CSF components in convalescent animals on the recovery from a motor deficit in recipients with a homotopic brain lesion]. / Vliianie razlichnykh komponentov likvora zhivotnykh-rekonvalistsentov na vosstanovlenie dvigatel'nogo defitsita u retsipientov s gomotopicheskim povrezhdeniem mozga.

The effect of the CSF components of the rats who had restored motor deficiency after left unilateral removal of motor neocortex, was studied in the rats with an analogous brain lesion. The first group of animals received a thermostable fraction of the donor CSF containing active factors of the posture asymmetry (FPA). The second group of animals were given a high-molecular fraction of the donor CSF with active factors inactivating the FPA. The first group revealed a significant acceleration of compensatory processes. Only a temporary positive effect was observed in the second group. The findings can be used in neurological clinics when treating motor disorders of central genesis.