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


METHODS
The effects of DHCA were analyzed in a neonatal piglet model with cardiopulmonary bypass, DHCA of 60 and 120 min and subsequent reperfusion of 6h. Complete histological analysis and changes in the mRNA expression of neuroglobin and cytoglobin were measured in the brain.


RESULTS
In 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.


CONCLUSIONS
Constitutive 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.
Schubert
Stephan
S
Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum, Berlin, Germany. sschubert@dhzb.de
Gerlach
Frank
F
Stoltenburg-Didinger
Gisela
G
Burmester
Thorsten
T
Hankeln
Thomas
T
Boettcher
Wolfgang
W
Wehsack
Anke
A
Hübler
Michael
M
Berger
Felix
F
Abdul-Khaliq
Hashim
H
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects* / Q000379:methods; D000078842:Cytoglobin; D004195:Disease Models, Animal; D005914:Globins / Q000032:analysis / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000517:prevention & control; D009410:Nerve Degeneration / Q000378:metabolism* / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D000078787:Neuroglobin; D034421:Sus scrofa
D000078842:Cytoglobin; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins