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NG2 and NG2‐positive cells delineate focal cerebral infarct demarcation in rats
Author(s) -
Claus Helene L.,
Walberer Maureen,
Simard Marie L.,
Emig Beata,
Muesken Sophia M.,
Rueger Maria A.,
Fink Gereon R.,
Schroeter Michael
Publication year - 2013
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2012.01322.x
Subject(s) - neun , ischemia , pathology , biology , extracellular matrix , neuroinflammation , microglia , lesion , necrosis , microbiology and biotechnology , neuroscience , anatomy , medicine , immunology , inflammation , immunohistochemistry , disease
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.