Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma
Guanghuan Wang, Xiaojun Yu, Dian Wang, Xiaohu Xu, Guang Chen, Xuewu Jiang
Department of Pediatric Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China (mainland)
Med Sci Monit 2015; 21:2613-2620
Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR).
MATERIAL AND METHODS: We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression.
RESULTS: Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A.
CONCLUSIONS: Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma.
Keywords: Brain - metabolism, Animals, Brain Stem - metabolism, Disease Models, Animal, Gene Expression Regulation, Multiple Organ Failure - blood, Neurons - drug effects, Oxidation-Reduction, Rabbits, Receptors, N-Methyl-D-Aspartate - metabolism, Spectrophotometry, Atomic, Time Factors, Wounds and Injuries - blood, Zinc - metabolism