期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 31, 期 1, 页码 172-178出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2012.1179
关键词
microglia; N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide; subacute cerebral ischemia; glial cell line-derived neurotrophic factor; tumor necrosis factor-alpha
资金
- Science and Research Foundation of National Institutes of Health [WKJ2008-2-031]
Microglia are the major immune cells in the central nervous system and play a key role in brain injury pathology. However, the role of activated microglia after subacute cerebral ischemia (SCI) remains unknown. To address this issue, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and treated pMCAO rats with N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (an inhibitor of microglial activation), or with vehicle alone. Finally, we determined the differences between the PJ34-and vehicle-treated rats with respect to neurological deficits, infarct volume, neuronal loss and the expression of CD11b (a marker of microglial activation), glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-alpha (TNF-alpha) at 1,3 and 7 days after treatment. We found that the PJ34-treated rats had more severe neurological deficits and a larger infarct volume and exhibited a decreased CD11b expression, more neuronal loss, decreased expression of GDNF mRNA and protein but increased expression of TNF-alpha mRNA and protein compared with the vehicle-treated rats at 3 and 7 days after treatment. These results indicate that activated microglia provide a neuroprotective role through balancing GDNF and TNF-alpha expression following SCI.
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