Increased neuroglobin levels in the cerebral cortex and serum after ischemia–reperfusion insults

Neuroglobin (NGB) is a newly discovered protein localized in neurons of the central and peripheral nervous systems in vertebrates. It functions to bind, store, and facilitate the utilization of oxygen in neuronal cells. Recent studies suggest that it may modulate hypoxic and ischemic injury. The major goal of the present study is to characterize the dynamic changes of NGB protein in the brain and serum in a global forebrain ischemia–reperfusion model using gerbils. The sensitivity and validity of serum NGB as a potential biomarker for brain injury were further evaluated. Global cerebral ischemia–reperfusion models were induced by bilateral carotid occlusion for 20 min followed with 2-, 8-, 16-, 24-, 48-, or 72-h reperfusion in forty-six Mongolian gerbils. Sham-operated and operated animals were sacrificed at the designated time after reperfusion. Brains were fixed for immunocytochemical study to evaluate the time-dependent expression of NGB, and the concentration of NGB in serum was measured by enzyme-linked immunosorbent assay. Our results showed that the expression of NGB was upregulated in the cerebral cortex but significantly downregulated in the hippocampus from 2 to 72 h of reperfusion after 20 min of bilateral common carotid arteries occlusion. The concentration of NGB in serum was significantly increased at 8 h and reached a peak at 48 h of reperfusion. There is a significant correlation between NGB levels in the serum and severity of neuronal damage in the gerbil brain. In summary, the upregulation of NGB in cerebral cortex and downregulation in hippocampus after reperfusion insults in the gerbil brain are consistent with the fact that cerebral cortex is more tolerant to hypoxic or ischemic injury than the hippocampus. Moreover, the changes of NGB levels in serum may be used to monitor the extent of brain damage in ischemic brain diseases.