Zhaohu Yuan*, Zhiwu Yu, Yiyu Zhang and Huikuan Yang Pages 955 - 963 ( 9 )
Background: Glial Maturation Factor Beta (GMFB) is a highly conserved brain-enriched protein implicated in immunoregulation, neuroplasticity and apoptosis, processes central to neural injury and repair following cerebral ischaemia. Therefore, we examined if changes in neurocellular GMFB expression and release can be used to assess brain injury following ischaemia.Methods and Results: Immunofluorescence staining, Western blotting, immunohistochemistry and ELISA were used to measure GMFB in cultured neurons and astrocytes, rat brain tissues and plasma samples from stroke model rats and stroke patients, while cell viability assays, TTC staining and micro- PET were used to assess neural cell death and infarct severity. Immunofluorescence and immunohistochemistry revealed GMFB expression mainly in astrocyte and neuronal nuclei but also in neuronal axons and dendrites. Free GMFB concentration increased progressively in the culture medium during hypoxia-hypoglycaemia treatment. Plasma GMFB concentration increased in rats subjected to middle cerebral artery occlusion (MCAO, a model of stroke-reperfusion) and in stroke patients. Plasma GMFB in MCAO model rats was strongly correlated with infarct size (R2=0.9582). Plasma GMFB concentration was also markedly elevated in stroke patients within 24 h of onset and remained elevated for more than one week. Conversely, plasma GMFB elevations were not significant in myocardial infarct patients and stroke patients without infarction. Conclusion: GMFB has the prerequisite stability, expression specificity and response dynamics to serve as a reliable indicator of ischaemic injury in animal models and stroke patients. Plasma GMFB may be a convenient non-invasive adjunct to neuroimaging for stroke diagnosis and prognosis.
Stroke, cerebral infarction, ischaemia-reperfusion injury, biomarker, Glia Maturation Factor Beta (GMFB), MCAO.
Department of Blood Transfusion, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong, Division of Laboratory Science, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, Department of Blood Transfusion, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong, Department of Blood Transfusion, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong