Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury

Abstract

Injury to the adult mammalian CNS results in reactive changes among the glial cells surrounding the site of damage. Recently, an unusual class of glial cells has been identified within the intact adult rat cerebellum on the basis of the expression of the NG2 chondroitin-sulfate proteoglycan (Levine and Card, 1987). To determine whether the cells that express the NG2 proteoglycan show reactive changes after injury, small puncture lesions were made into the cerebelli of adult rats, and changes among astrocytes, microglia and NG2-positive cells were examined using immunohistochemical staining with cell type-specific marker antibodies. Beginning at 24 hr after lesion, NG2-positive cells immediately adjacent to the lesion site bound the anti-NG2 antibodies more heavily than cells within the undamaged areas of the cerebellum. This increase in anti-NG2 immunoreactivity was transient, reaching a maximum at 7 d postlesion and declining slowly thereafter. The increase in anti-NG2 immunoreactivity was accompanied by an increase in the levels of mRNA encoding the NG2 core protein as demonstrated by in situ hybridization. NG2-positive cells adjacent to the lesion site incorporated 3H-thymidine into their nuclei beginning at 24 hr postlesion and increased in number. Concurrent with these changes, microglia became activated and increased in number, monocytes invaded the damaged tissue, and an astrocytic scar formed. These observations demonstrate that the cells that express the NG2 proteoglycan are a reactive cell type that responds to brain injury. The increased expression of the NG2 chondroitin-sulfate proteoglycan may contribute to the failure of damaged CNS axons to regenerate successfully.

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

“…The NG2 proteoglycan is increased after CNS injury by oligodendrocyte precursor cells (Levine, 1994;Rhodes et al, 2006), phosphacan is upregulated within glial scars (McKeon, et al, 1995), and phosphacan, brevican, versican, and neurocan are all produced within the injured spinal cord (Jones, et al, 2003a). Chondroitin sulfate proteoglycans are found in the brain after stab wound (Fitch and Silver, 1997a), in the spinal cord after injury to the dorsal root (Pindzola et al, 1993), and in the spinal cord following injury (Fitch and Silver, 1997a;Jones, et al, 2003a;Jones et al, 2003b).…”

Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat

“…During neural development, CSPGs regulate axon growth and pathfinding (Snow et al, 1990;Jhaveri, 1993). After injury in the adult, they are enriched in scar tissues (McKeon et al, 1991;Levine, 1994;Lemons et al, 1999;Properzi et al, 2005), in which they contribute to hampering axon regeneration (Davies et al, 1997;Moon et al, 2001;Bradbury et al, 2002;Grimpe and Silver, 2002;Jones and Tuszynski, 2002) or compensatory sprouting (Tropea et al, 2003). In addition, several studies have highlighted their role in controlling structural plasticity in the absence of injury (Brakebusch et al, 2002;Pizzorusso et al, 2002;Miyata et al, 2004).…”

The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat

“…Tsiperson et al (2015) also demonstrated that following demyelination by cuprizone, an increase in PDGFR␣ progenitors was observed in wild mice as a result of increased DNA synthesis and cell proliferation. According to Decker et al (2002), cytokines and growth factors released either from widespread inflammatory and glial cells (Levine, 1994) or from damaged axons after demyelination (Di Bello et al, 1999), induce OPCs to reenter the cell cycle after demyelination.…”