NG2 and NG2-positive cells delineate focal cerebral infarct demarcation in rats.
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.
Department of Neurology, University Hospital Max-Planck-Institute for Neurological Research, Cologne Institute of Neuroscience and Medicine (INM-3), Cognitive Neurology Section, Research Centre Juelich, Juelich, Germany.
Helene L
HL
Claus
Maureen
M
Walberer
Marie L
ML
Simard
Beata
B
Emig
Sophia M
SM
Muesken
Maria A
MA
Rueger
Gereon R
GR
Fink
Michael
M
Schroeter
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D034961:Antigens, Nuclear / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009336:Necrosis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000099216:Chondroitin Sulfate Proteoglycan 4
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000941:Antigens; D034961:Antigens, Nuclear; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C100745:Aif1 protein, rat; C546339:Rbfox3 protein, rat