Department of Blood Transfusion, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong, China.
Division of Laboratory Science, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China.
Curr Pharm Biotechnol. 2020;21(10):955-963. doi: 10.2174/1389201021666200210102425.
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.
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.
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.
神经胶质细胞成熟因子-β（GMFB）是一种高度保守的脑富集蛋白，与免疫调节、神经可塑性和细胞凋亡有关，这些过程是脑缺血后神经损伤和修复的核心。因此，我们研究了神经细胞 GMFB 表达和释放的变化是否可用于评估缺血后的脑损伤。
免疫荧光染色、Western blot、免疫组化和 ELISA 用于测量培养神经元和星形胶质细胞、脑缺血模型大鼠和脑卒中患者脑组织和血浆样本中的 GMFB，同时细胞活力测定、TTC 染色和 micro-PET 用于评估神经细胞死亡和梗死严重程度。免疫荧光和免疫组化显示 GMFB 表达主要在星形胶质细胞和神经元核中，但也在神经元轴突和树突中。缺氧低糖处理过程中，GMFB 在培养基中的游离浓度逐渐增加。大脑中动脉闭塞（MCAO，脑卒中再灌注模型）大鼠和脑卒中患者的血浆 GMFB 浓度增加。MCAO 模型大鼠的血浆 GMFB 与梗死面积呈强相关性（R2=0.9582）。脑卒中患者发病后 24 小时内，血浆 GMFB 浓度明显升高，并持续升高超过一周。相反，心肌梗死患者和无梗死脑卒中患者的血浆 GMFB 升高不显著。
GMFB 具有稳定性、表达特异性和反应动力学的先决条件，可作为动物模型和脑卒中患者缺血性损伤的可靠指标。血浆 GMFB 可能是脑卒中诊断和预后神经影像学的一种方便的非侵入性辅助手段。
