Increase of NG2-positive cells associated with radial glia following traumatic spinal cord injury in adult rats

Abstract

In the CSN including the spinal cord, NG2 proteoglycan is a marker of oligodendrocyte progenitors. To elucidate the dynamics of the endogenous neural stem (progenitor) cells in adult rats with spinal cord injury (SCI), we examined an immunohistochemical analysis of NG2, GFAP, and 3CB2, a specific marker of radial glia (RG). SD rats were divided into a SCI group (n = 25) and a sham-operated group (n = 5). In the injury group, laminectomy was performed at Th11-12 and contusive compression injury was created by applying a weight of 30 g for 10 min. Rats were sacrificed at 24 h, and 1, 4, 8 and 12 weeks post-injury. Frozen 20-mu m sections of tissue 5 and 10 mm rostral and caudal to the epicenter of injury were prepared. Immunohistochemistry was performed using antibodies against NG2, GFAP and 3CB2. At 4 weeks after injury, NG2-positive glial cells arose from below the pial surface as bipolar cells with processes extending throughout the entire white matter. NG2 expression peaked at 4 weeks after injury, showing a 7-fold increase compared to the 24 h after injury. The NG2-positive cells with processes which increased in the white matter of the spinal cord were GFAP-positive and also co-localized with 3CB2 antigen. The pattern of NG2 expression of these cells was temporally and spatially different from the pattern of NG2 expression that accumulated around the hemorrhagic and necrotic epicenter. These results suggest that NG2 positive cells which derived from subpial layer, may have some lineage to RG after SCI in adult rodents.

Induction of angiopoietin-2 after spinal cord injury

“…Although SCI did not induce Ang-2 in ependymal or subependymal spinal cord cells, which are analogous to the subventricular neural stem cells (Kulbatski et al, 2005), we found Ang-2 in NG2 cells that morphologically closely resemble white matter-specific NG2-positive oligodendrocyte progenitor cells (OPCs), characterized and described in the study by Wu et al, (2005). It has been well established that NG2-labeled OPCs generate myelinating oligodendrocytes (Horner et al 2000; Nishiyama et al 2002; Reynolds et al 2002), whose contribution to the functional recovery after SCI is well established (Cao et al, 2010; Jiang et al, 2008).…”

“…Here we show lateral white matter of a spinal cord cross section with cells that morphologically resembled GFAP-positive radial glia activated after SCI (Wu et al, 2005). Calibration line: 20 μm.…”

Adult Spinal Cord Radial Glia Display a Unique Progenitor Phenotype

“…Recently, radially-arrayed WM GFAP + cells have been reported to become mitotic and up-regulate developmental gene expression (e.g. nestin, BLBP, vimentin) following autoimmune demyelination or contusive SC injury [14], [15], [16], [17], concurrent with an accumulation of oligodendrocyte precursors in the sub-pial region [18]. It is thus possible that a secondary, uncharacterized, neural progenitor population resides in the sub-pial WM of the adult SC, whose molecular identity has yet to be established.…”

Regional heterogeneity in astrocyte responses following contusive spinal cord injury in mice

“…Astrocytes responding to SCI arise from a variety of sources, including mature cells near the lesion and progenitors that reside both in the parenchyma and in the ependymal zone surrounding the central canal (Johansson et al, 1999; Yamamoto et al, 2001; Mothe and Tator, 2005; Wu et al, 2005; Horky et al, 2006; Meletis et al, 2008; Sellers et al, 2009). The peak of cell proliferation occurs in the first week after a contusive SCI, and newborn neural progenitor cells differentiate almost exclusively into glial cells (McTigue et al, 2001; Lytle and Wrathall, 2007; Mothe et al, 2008).…”