Protein S-100β in Brain and Serum after Deep Hypothermic Circulatory Arrest in Rabbits: Relationship to Perivascular Astrocytic Swelling

Abstract

The aim of this study was to evaluate the relationship between the kinetic patterns of the protein S-100beta, an astroglial cell marker, and its immunohistochemical expression in the brain in rabbits that underwent cardiopulmonary bypass with deep hypothermic circulatory arrest. Fourteen New Zealand rabbits (weight, 3.1+/-0.25 kg) were anaesthetised, intubated and mechanically ventilated. Four animals were not connected to the cardiopulmonary bypass and served as controls. Ten animals were perfused according to a uniform protocol. After systemic cooling, deep hypothermic circulatory arrest was induced for 60 minutes. After reperfusion and rewarming, the animals were weaned from bypass and sacrificed. In the brain, astrocyte reactivity for S-100beta was evaluated immunocytochemically (DPC Immustain) and the serum concentrations of S-100beta were analysed using a commercially available immunoluminometric kit (Byk-Sangtec, Dietzenbach, Germany). In all experimental animals a significant increase of the serum concentration of the protein S-100beta was found immediately after reperfusion and the termination of cardiopulmonary bypass. In comparison with the control animals, increased staining of S-100beta was found in the astroglial cells and swollen astrocytic end-feet in the perivascular regions. There were fewer signs of neuronal cell injury of neurones in the hippocampus structure. In conclusion, astrocytic activation and S-100beta overexpression seems to precede the neurodegeneration following deep hypothermic circulatory arrest. The marked perivascular cell swelling may support the assumption of reperfusion injury of the astroglial cell complex that forms the blood-brain barrier, which may be indicative of the source of the released S-100beta into the blood stream.

S100B is increased in mood disorders and may be reduced by antidepressive treatment

“…On the one hand, S100B might be increased due to injury of astrocytes and a disrupted integrity of the blood-brain barrier, as S100B, with a mol. wt of 10 kDa, may not pass through the intact blood-brain barrier [4,5]. This assumption is supported by studies showing reduced volumes [6,7], and diminished densities of glial cells [8,21,22] in several brain regions in mood disorders.…”

“…Nanomolar concentrations act as growth and/or differentiation factor for neurons and astrocytes, whereas micromolar concentrations may induce apoptosis, for instance in pheochromocytoma cells. Serum S100B has been used as a marker for structural damage to the brain, particularly to astrocytes, for instance after cardiopulmonary bypass [4] and severe head injury [5]. Increased serum S100B levels may be due to leakage of the astrocytic membrane [4].…”

“…In summary, serum levels of S100B may be a suitable marker for damage to the brain, and particularly for alterations of astrocytes [4]. Moreover, in mood disorders cerebral morphological abnormalities are known that include reduction of glial cells [8] and alteration of astrocytes [9], in areas of the prefrontal cortex.…”

Propofol offers no advantage over isoflurane anesthesia for cerebral protection during cardiopulmonary bypass: a preliminary study of S-100ß protein levels

“…4,5 The appearance of S-100ß in serum indicates both neuronal damage and increased permeability of the blood-brain barrier. 6 Neuropsychological testing is one of the best methods currently available for assessing changes in intellectual function after a cerebral insult and has identified persistent mild, moderate or severe deterioration in 19% to 38% of patients who undergo CPB. 7 Although proposal of mechanisms by which anesthetics or other drugs may produce cerebral protection are controversial and changing rapidly, isoflurane and propofol have been shown to decrease neuronal injury during ischemia by decreasing cerebral oxygen consumption.…”

NMDA Receptor Antibodies Predict Adverse Neurological Outcome After Cardiac Surgery in High-Risk Patients

“…Astroglia together with endothelial cells act as a supply and protective barrier between the cerebral microvasculature and the neurons. 19 The biological function of S100B is largely unknown, but its release into the blood stream appears to be associated with functional disturbance and increased permeability of the blood-brain barrier (BBB). 20 Seizures, stroke, head trauma, inflammation and CPB have all been shown to cause dysfunction of the BBB accompanied by increased serum S100B concentrations.…”