2nd International Symposium on the Pathophysiology of Cardiopulmonary Bypass. Neurological complications after surgery
- Meeting abstract
Early immunohistochemical brain overexpression of S-100β and increased serum level after deep hypothermic circulatory arrest in rabbits: relationship to perivascular astrocytic swelling
Critical Care volume 4, Article number: P1 (2000)
Understanding the pathophysiology and neuropathological changes that might be related to brain injury after surgical cardiac procedures using hypothermic cardiopulmonary bypass (CPB) with a period of circulatory arrest (TCA) is fundamental to the development of hemodynamic and pharmacological neuroprotective interventions. Therefore, the aim of this study was to evaluate the relationship between the regional immunohistochemical expression of S-100β in the brain and the serum kinetic patterns in rabbits undergoing CPB with a 60-minute period of TCA, followed by reperfusion and rewarming.
Fourteen New Zealand rabbits (body weight 3.1 ± 0.25 kg) were anaesthetised, intubated and mechanically ventilated. Four animals were not connected to the CPB and were used as controls. Ten animals were perfused after aortic and right atrial cannulation according to a uniform protocol: full-flow CPB (150-200 mL/kg per min), PCO2 uncorrected for hypothermia (α-stat blood gas management). After surface cooling and the establishment of a hypothermic rectal temperature of 14 °C, TCA was induced for 60min. The animals were then reperfused and rewarmed over 60 min to achieve a normal rectal temperature of 38 °C. The animals were weaned from bypass and killed. The brain was immediately removed, cut in standardized sections and fixed in formaldehyde. Astrocyte reactivity was evaluated immunocytochemically by the use of monoclonal mouse primary antibodies to S-100β protein (DPC Immustain, code CKS1S). The serum concentrations of S-100β were analysed using a commercially available LIA kit (Byk-Sangtec, Dietzenbach, Germany)
In all experimental animals a significant increase of the serum concentration of the astrocytic protein S-100β was found immediately after reperfusion and the termination of CPB. In comparison with the control animals increased expression of S-100β was found in the astroglial cells and astrocytic dendrites in the perivascular regions. A distinctive pathognomonic morphological cell injury that exhibited a marked swelling of the perivascular astrocytic cell dendrites were also found by electron microscopy from the cerebral capillaries in the hypocamppus in the experimental animals. There were less signs of neuronal cell injury of neurons in the hippocampus formation.
Astrocytic activation and S-100β overexpression seem to precede the neurodegeneration following global cold ischemia. The marked perivascular cell swelling may support the assumption of reperfusion injury of the astroglial cell complex that forms the blood-brain barrier (BBB), which may be indicative of the source of the released S-100β into the bloodstream. The early significant increased serum levels of S-100β may provide information on possible ongoing related injury in neuronal cell in patients after cardiac surgery as well, who potentially benefit from neuroprotective interventions. The function and exact release mechanism of the S-100β through the BBB into the blood in this respect, however, need further explanation.
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Abdul-Khaliq, H., Schubert, S., Stoltenburg-Didinger, G. et al. Early immunohistochemical brain overexpression of S-100β and increased serum level after deep hypothermic circulatory arrest in rabbits: relationship to perivascular astrocytic swelling. Crit Care 4 (Suppl 4), P1 (2000). https://doi.org/10.1186/cc674