Neuroscience Graduate Studies Program.
Nationwide Children's Hospital, Columbus, Ohio 43205.
J Neurosci. 2015 Jan 21;35(3):1274-90. doi: 10.1523/JNEUROSCI.2568-14.2015.
Adult progenitor cells proliferate in the acutely injured spinal cord and their progeny differentiate into new oligodendrocytes (OLs) that remyelinate spared axons. Whether this endogenous repair continues beyond the first week postinjury (wpi), however, is unknown. Identifying the duration of this response is essential for guiding therapies targeting improved recovery from spinal cord injury (SCI) by enhancing OL survival and/or remyelination. Here, we used two PDGFRα-reporter mouse lines and rats injected with a GFP-retrovirus to assess progenitor fate through 80 d after injury. Surprisingly, new OLs were generated as late as 3 months after injury and their processes ensheathed axons near and distal to the lesion, colocalized with MBP, and abutted Caspr+ profiles, suggesting newly formed myelin. Semithin sections confirmed stereotypical thin OL remyelination and few bare axons at 10 wpi, indicating that demyelination is relatively rare. Astrocytes in chronic tissue expressed the pro-OL differentiation and survival factors CNTF and FGF-2. In addition, pSTAT3+ NG2 cells were present through at least 5 wpi, revealing active signaling of the Jak/STAT pathway in these cells. The progenitor cell fate genes Sox11, Hes5, Id2, Id4, BMP2, and BMP4 were dynamically regulated for at least 4 wpi. Collectively, these data verify that the chronically injured spinal cord is highly dynamic. Endogenous repair, including oligodendrogenesis and remyelination, continues for several months after SCI, potentially in response to growth factors and/or transcription factor changes. Identifying and understanding spontaneous repair processes such as these is important so that beneficial plasticity is not inadvertently interrupted and effort is not exerted to needlessly duplicate ongoing spontaneous repair.
成年祖细胞在急性损伤的脊髓中增殖，其后代分化为新的少突胶质细胞（OLs），对未受损的轴突进行髓鞘修复。然而，这种内源性修复是否会持续到损伤后第一周（wpi）以外，目前尚不清楚。确定这种反应的持续时间对于指导通过增强 OL 存活和/或髓鞘修复来改善脊髓损伤（SCI）后的恢复的治疗方法至关重要。在这里，我们使用了两种 PDGFRα-报告小鼠系和用 GFP-逆转录病毒注射的大鼠，通过损伤后 80 天评估祖细胞的命运。令人惊讶的是，新的 OL 甚至在损伤后 3 个月产生，它们的突起包绕着损伤部位附近和远处的轴突，与 MBP 共定位，并与 Caspr+ 结构相邻，表明形成了新的髓鞘。半薄切片证实了 10 wpi 时典型的薄 OL 髓鞘形成和很少的裸露轴突，表明脱髓鞘相对较少。慢性组织中的星形胶质细胞表达 OL 分化和存活因子 CNTF 和 FGF-2。此外，pSTAT3+NG2 细胞至少在 5 wpi 时存在，表明 Jak/STAT 通路在这些细胞中活跃。祖细胞命运基因 Sox11、Hes5、Id2、Id4、BMP2 和 BMP4 至少在 4 wpi 内被动态调节。总的来说，这些数据证实了慢性损伤的脊髓是高度动态的。内源性修复，包括少突胶质细胞生成和髓鞘修复，在 SCI 后可持续数月，可能是对生长因子和/或转录因子变化的反应。识别和理解这种自发修复过程非常重要，这样有益的可塑性就不会被无意中打断，也不会费力去不必要地复制正在进行的自发修复。
