NG2 and NG2-positive cells delineate focal cerebral infarct demarcation in rats

被引:19
作者
Claus, Helene L. [1 ,2 ]
Walberer, Maureen [1 ,2 ]
Simard, Marie L. [1 ,2 ]
Emig, Beata [1 ]
Muesken, Sophia M. [1 ]
Rueger, Maria A. [1 ,2 ]
Fink, Gereon R. [1 ,3 ]
Schroeter, Michael [1 ,2 ]
机构
[1] Univ Hosp Cologne, Dept Neurol, D-50924 Cologne, Germany
[2] Max Planck Inst Neurol Res, D-50931 Cologne, Germany
[3] Res Ctr, Inst Neurosci & Med INM 3, Cognit Neurol Sect, Julich, Germany
关键词
focal cerebral ischemia; infarct demarcation; microglia; neuroinflammation; NG2; secondary neurodegeneration; CHONDROITIN-SULFATE PROTEOGLYCAN; SPINAL-CORD-INJURY; GLIAL-CELLS; NEURITE GROWTH; BRAIN-INJURY; OLIGODENDROCYTES; MACROPHAGES; PLASTICITY; LINEAGE; NEURODEGENERATION;
D O I
10.1111/j.1440-1789.2012.01322.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Focal cerebral ischemia induces cellular responses that may result in secondary tissue damage. We recently demonstrated multi-facetted spatial and temporal patterns of neuroinflammation by multimodal imaging. In the present study, we especially focus on the separation of vital and necrotic tissue, which enabled us to define a demarcation zone. Focal cerebral ischemia was induced via macrosphere embolization of the middle cerebral artery in Wistar rats. Subsequent cellular processes were investigated immunohistochemically from 3 to 56 days after onset of ischemia. We detected several infarct subareas: a necrotic infarct core and its margin adjacent to a nerve/glial antigen 2 (NG2)+ zone delineating it from a vital peri-infarct zone. Initially transition from necrotic to vital tissue was gradual; later on necrosis was precisely separated from vital tissue by a narrow NG2+ belt that was devoid of astrocytes, oligodendrocytes or neurons. Within this demarcation zone NG2+ cells associate with ionized calcium binding adaptor molecule 1 (Iba1) but not with GFAP, neuronal nuclear antigen (NeuN) or 2, 3-cyclic nucleotide 3-phosphodiesterase (CNPase). During further infarct maturation NG2 seemed to be positioned in the extracellular matrix (ECM) of the demarcation zone, whereas Iba1+ cells invaded the necrotic infarct core and GFAP+ cells built a gliotic containing belt between the lesion and NeuN+ unaffected tissue. Overall, our data suggested that NG2 proteoglycan expression and secretion hallmarked demarcation as a process that actively separated necrosis from vital tissue and therefore decisively impacts secondary neurodegeneration after ischemic stroke.
引用
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页码:30 / 38
页数:9
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