Cerebral expression of neuroglobin and cytoglobin after deep hypothermic circulatory arrest in neonatal piglets

IntroductionDeep hypothermic circulatory arrest (DHCA) is used in corrective cardiac surgery for complex congenital heart disease. Endogenous protective mechanisms may be responsible for the prevention of brain damage after hypothermic ischemia. Neuroglobin and cytoglobin are expressed in brain cells and appear to modulate hypoxic-ischemic brain injury. However, their neuroprotective potency is still not understood. Thus the aim of this study was to detect the influence exerted by DHCA on their expression.MethodsThe effects of DHCA were analyzed in a neonatal piglet model with cardiopulmonary bypass, DHCA of 60 and 120 min and subsequent reperfusion of 6 h. Complete histological analysis and changes in the mRNA expression of neuroglobin and cytoglobin were measured in the brain.ResultsIn comparison to animals without DHCA, neuroglobin expression was stable after 60 min DHCA and neuronal cell necrosis in the cortex was mild (< 10 %). Neuroglobin expression was significantly reduced after 120 min DHCA, which was accompanied by substantial neuronal cell necrosis (> 50 %). Cytoglobin expression did not differ significantly between animals with neuronal necrosis vs. sham.ConclusionConstitutive expression levels of neuroglobin may explain the mild neuronal injury after 60 min DHCA. Significant neuronal cell death correlates with reduced neuroglobin expression and might reflect a limited capacity to compensate for ischemic injury. Both respiratory cell proteins may constitute attractive targets for therapeutic modulation of gene regulation, but further studies are necessary.

Research Highlights
► Neuroglobin expression was significant reduced after 120 min of deep hypothermic circulatory arrest (DHCA).
► Neuronal cell death correlates with reduced neuroglobin expression.
► Neuroglobin might play a significant role in the prevention of neuronal cell death after circulatory arrest.