NG2 is a type I transmembrane glycoprotein known as chondroitin sulfate proteoglycan 4 (CSPG4). In the healthy central nervous system, NG2 is exclusively expressed by oligodendrocyte progenitor cells and by vasculature pericytes. A large body of immunohistochemical studies showed that under pathological conditions such as acute brain injuries and experimental autoimmune encephalomyelitis (EAE), a number of activated microglia were NG2 immuno-positive, suggesting NG2 expression in these cells. Alternative explanations for the microglial NG2 labeling consider the biochemical properties of NG2 or the phagocytic activity of activated microglia. Reportedly, the transmembrane NG2 proteoglycan can be cleaved by a variety of proteases to deposit the NG2 ectodomain into the extracellular matrix. The ectodomain, however, could also stick to the microglial surface. Since microglia are phagocytic cells engulfing debris of dying cells, it is difficult to identify a genuine expression of NG2. Recent studies showing (1) pericytes giving rise to microglial after stroke, and (2) immune cells of NG2-EYFP knock-in mice lacking NG2 expression in an EAE model generated doubts for the de novo expression of NG2 in microglia after acute brain injuries. In the current study, we took advantage of three knock-in mouse lines (NG2-CreERT2, CX 3 CR 1 -EGFP and NG2-EYFP) to study NG2 expression indicated by transgenic fluorescent proteins in microglia after tMCAO (transient middle cerebral artery occlusion) or cortical stab wound injury (SWI). We provide strong evidence that NG2-expressing cells, including OPCs and pericytes, did not differentiate into microglia after acute brain injuries, whereas activated microglia did express NG2 in a disease-dependent manner. A subset of microglia continuously activated the NG2 gene at least within the first week after tMCAO, whereas within 3 days after SWI a limited number of microglia at the lesion site transiently expressed NG2. Immunohistochemical studies demonstrated that these microglia with NG2 gene activity also synthesized the NG2 protein, suggesting activated microglia as an additional source of the NG2 proteoglycan after acute brain injuries. Electronic supplementary material The online version of this article (10.1186/s40478-020-01016-2) contains supplementary material, which is available to authorized users.
The empirical investigation of several geophysical time series indicates that they are composed of segments representing diferent natural regimes, or periods when events are strongly autocorrelated. Using a data transformation method developed b y Hurst, these regimes are diferentiated b y rescaling the time series and examining the resulting transformed trace for inflections. As regime signals are not completely mixed and have rather long run lengths, Hurst rescaling produces a clustering of extremes of the same sign and elevates the Hurst exponent to values greater than 0.5. These regimes have a characteristic distribution, as dejined b y the mean and standard deviation, which difer f r o m the statistical characteristics of the complete record. Analysis of sunspot numbers, monthly precipitation records f r o m the midwestern United States, and annual watershed discharge yield regimes that correlate to well-documented periods of extreme activity. Rescaling appears to be useful in screening time series of unknown characteristics to diferentiate periods dominated b y regime-specijic physical processes .
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