Research on overactivation of poly(adenosine phosphate-ribose) polymerase 1 and molecular events in neuronal injury after deep hypothermic circulatory arrest

doi:10.3760/cma.j.issn.1673-4777.2009.12.001

Abstract：Objective To investigate the molecular mechanism of brain injury after deep hypothermic circu-latory arrest (DHCA) and identify the molecular events through cellular energy failure, excitotoxicity, and overacti-ration of poly(adenosine diphosphate-ribose) polymerase 1 in brain tissues of a rabbit model of DHCA. Methods We established 2 models of eardiopulmonary bypass (CPB) and DHCA associated with cerebral microdialysia in rab-bits. DHCA lasted for 60 minutes. The measurements of glucose, lactate, pyruvate, and glutamate collected by means of micredialysis were quantified by using high-performance liquid chromatography. The overactivation of poly (adenosine diphosphate-ribose) polymerase 1 was assessed by detecting immunostaining of poly(adenosine diphos-phate-ribose). Histologic studies were used to identify neuronal morphologic changes and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining was used to identify apoptotic cells. Results DHCA significantly increased the lactate/pyruvate and lactate/glucose ratios and the glutamate value, whereas CPB did not (P<0.05). DHCA significantly increased the numbers of poly (adenosine diphosphate-ri-bose)-positive and apoptotic neurons compared with CPB (P<0.05). More injured neurons were found in the DHCA (histologic scores, P<0.05). Conclusions This study demonstrated that there were molecular events con-sisting of cellular energy failure, excitotoxicity, overactivation of poly (adenosine diphosphate-ribose) polymerase 1, and necrosis and/or apoptosis in brain injury after DHCA, which altogether contributed to brain injury.