NG2-Glia Transiently Overcome Their Homeostatic Network and Contribute to Wound Closure After Brain Injury

Abstract

In the adult brain, NG2-glia represent a cell population that responds to injury. To further investigate if, how and why NG2-glia are recruited to the injury site, we analyzed in detail the long-term reaction of NG2-glia after a lesion by time-lapse two-photon in vivo microscopy. Live imaging over several weeks of GFP-labeled NG2-glia in the stab wounded cerebral cortex revealed their fast and heterogeneous reaction, including proliferation, migration, polarization, hypertrophy, or a mixed response, while a small subset of cells remained unresponsive. At the peak of the reaction, 2–4 days after the injury, NG2-glia accumulated around and within the lesion core, overcoming the homeostatic control of their density, which normalized back to physiological conditions only 4 weeks after the insult. Genetic ablation of proliferating NG2-glia demonstrated that this accumulation contributed beneficially to wound closure. Thus, NG2-glia show a fast response to traumatic brain injury (TBI) and participate in tissue repair.

Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain

“…Strikingly, oligodendrocyte progenitor cells (OPCs) react to insults such as demyelination [20,21], traumatic brain injury (TBI) [22], or neurodegenerative disorders [23] as fast as the residential microglial cells. In physiological conditions these slow proliferating progenitors display very limited and short-range migration [24,25] and maintain their nonoverlapping cellular domains by balancing cellular proliferation and cell death [22,[24][25][26][27]. However, a rapid and heterogeneous reaction of OPCs has been documented in response to brain injury [22,24,25,28].…”

Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism

“…NG2 glia are present in all regions of the brain between postnatal development and death, and provide beneficial support during different damages and diseases of the central nervous system [ 15 , 60 ]. After traumatic injury, for example, these cells react very fast, migrate to the damaged area and contribute to wound closure [ 18 , 61 , 62 ]. This function was accelerated by increased levels of Grx2c ( Fig.…”

“…First discovered in the beginning of the 1980s [ 16 , 17 ], NG2 glia are known today to have important functions in the pathological context, e.g. wound closure [ 18 ] and remyelination [ 19 ] in the adult brain. However, NG2 glia have been suggested as possible cells of orgin of distinct types of gliomas, including glioblastomas and oligodendrogliomas [ 20 , 21 ].…”

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

“…Proliferation Yes, Gradual Decline [112] Yes, High [111] Yes, Low [109] Yes, High [57] Yes, High [113] Yes, High [57] Yes, High [114] Yes, High [115] Differentiation Yes, Medium [112] Yes, Medium [106] Yes, Medium [116] Yes, Medium [57] Yes, Low [106] Yes [115] Migration Yes, Medium [112] Yes [113] Yes [57] Yes [116] Yes [115] Quiescence Yes, Low [116] Possibly [21] No [113] No [114] Decrease [117] Glial Scar Formation N/A Yes [57] Yes, 25% [58] Yes [116] Yes, 5% [58] Yes, 5-8% [58] Yes [115] Neural Lesion N/A Yes, High [113] Yes, Delayed increase [118] Yes [114] Yes [118] Yes [115] Ependymal and NG2+ cell stem-like behaviors in the normal physiology and after different types of SCI.…”