Distribution and differentiation of A2B5+ glial precursors in the developing rat spinal cord

In many regions of the rat central nervous system, oligodendrocytes develop from migratory A2B5⁺ precursor cells. In the rat spinal cord, during early embryonic development the capacity for oligodendrogenesis appears to be restricted to ventral regions of the spinal cord, while cultures of postnatal rat spinal cord contain a distinct population of A2B5⁺ astrocyte precursors. To determine if, as in other regions of the CNS, spinal cord A2B5⁺ cells give rise directly to oligodendrocytes and astrocytes, the initial distribution, and subsequent dispersion, proliferation, and differentiation of spinal cord A2B5⁺ cells have been examined in both explant and dissociated cell cultures. Spinal cord oligodendrocytes develop from A2B5⁺ cells. At E14, A2B5⁺ cells are restricted to ventral regions of the spinal cord and as development proceeds they become more uniformly distributed throughout the spinal cord. In explant cultures, greater than 95% of the explants that contain oligodendrocytes also contain A2B5⁺ cells and a proportion of mature oligodendrocytes retain detectable A2B5 immunoreactivity briefly on their surface. The maturation of spinal cord oligodendrocyte precursors occurs in a number of distinct stages characterized by the expression of O4 immunoreactivity, which first appears at E16, and GC immunoreactivity, which first appears at E18. As spinal cord oligodendrocyte precursors acquire O4 immunoreactivity they appear to lose the ability to proliferate in response to PDGF but retain the ability to proliferate in response to bFGF, suggesting that the control of proliferation of oligodendrocyte precursors is, in part, dependent on their maturational state. In the presence of high serum, spinal cord A2B5⁺ cells fail to develop in isolated E14 dorsal spinal cord cultures, while in ventral cultures they subsequently differentiate into A2B5⁺ astrocytes suggesting that A2B5⁺ astrocyte precursors are also initially ventrally located. Unlike oligodendrocyte differentiation, however, the differentiation of spinal cord A2B5⁺ cells into astrocytes is delayed in early embryonic-derived cultures compared to those from older animals. These observations suggest that local influences may regulate the timing of spinal cord A2B5⁺ astrocyte development, but not spinal cord oligodendrocyte development. © 1994 Wiley-Liss, Inc.     

Spinal Cord Contusion

Spinal cord injury is a major cause of disability with devastating neurological outcomes and lim-ited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.     

脊髓半切后损伤区周围ERK1／2活性的改变

目的 观察大鼠脊髓半切后ERK1/2活性的变化及发生变化的细胞类型。方法 大鼠行脊髓半横断术后3d，用免疫组织化学法和免疫荧光双标记法观察磷酸化ERK1/2的变化及其与各种神经细胞标记物的共存状况。结果 观察到脊髓半切3d大鼠的ERK1/2磷酸化程度明显升高。阳性细胞为分布于邻近损伤区周围的具有短突起的小胞体细胞。双标记表明其中的大部分阳性细胞为小胶质细胞和寡突胶质细胞。结论 本研究提示脊髓半横断3d，ERKl/2参与了小胶质细胞和寡突胶质细胞的活化，有可能在脊髓损伤的/继发性过程中具有重要作用。     

Rolipram联合少突胶质前体细胞移植治疗大鼠脊髓损伤

背景：脊髓损伤轴突难以再生涉及到多方面原因,综合运用多种治疗方法应该更有效。目的：应用Rolipram联合少突胶质前体细胞移植治疗大鼠脊髓损伤,观察轴突再生和再髓鞘化的情况。方法：Wistar大鼠利用ALLEN法打击形成脊髓损伤模型。Rolipram治疗组和联合治疗组背部皮下埋置ALZET渗透性微泵内装Rolipram 200 μL,每小时释放0.5 μL,2 mg/(kg•d),可持续14 d,1周后局部注入0.012 5 μmol 的双丁酸环腺苷酸;细胞移植组和联合治疗组移植少突胶质前体细胞,脊髓损伤组注入同等量的生理盐水,术后每周测定BBB运动评分,4周取材,冰冻切片,苏木精-伊红染色,免疫荧光染色。结果与结论：伤后4周Rolipram治疗组和联合治疗组BBB运动评分高于脊髓损伤组和细胞移植组;免疫荧光显示Rolipram治疗组和联合治疗组损伤局部NF200表达旺盛;细胞移植组和联合治疗组少突胶质前体细胞存活并表达髓鞘碱性蛋白,后者存活数量更多,并且有髓纤维增多。说明应用Rolipram提高环磷腺苷水平促进了大鼠脊髓损伤功能的恢复,联合少突胶质前体细胞移植可产生协同促进作用。     

Delayed glial cell death following wallerian degeneration in white matter tracts after spinal cord dorsal column cordotomy in adult rats

The devastating consequences of spinal cord injury (SCI) result primarily from damage to long tracts in the spinal white matter. To elucidate the secondary injury processes occurring after SCI, we investigated the relationship between apoptosis and Wallerian degeneration in spinal white matter tracts. In the rat spinal cord, the corticospinal tract (CST) and the dorsal ascending tract (DAT) are separated from each other in the dorsal column and relay information in opposite directions. A dorsal column cordotomy at the eighth thoracic (T8) level simultaneously induces Wallerian degeneration in the CST caudal to and in the DAT rostral to the injury. Using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, we demonstrate that apoptosis occurred in areas of Wallerian degeneration in both tracts throughout the length of the cord segments studied (from T3 to T12). This delayed cell death, more apparent in the DAT, began at 7 days after injury and peaked at 14 days for the DAT and 28 days for the CST. Although a few TUNEL+ cells, slightly above the noninjury control level, were found in intact areas of both tracts, statistically significant differences in the number of TUNEL+ cells were found between the intact and the lesioned tract segments (CST, F < 0.01; DAT, F < 0.001). Within a particular spinal segment, a mean number of 64 and 939 TUNEL+ cells in the degenerating CST and DAT, respectively, were estimated stereologically at 14 days postinjury. TUNEL+ cells in degenerating tracts outnumber their intact counterparts by 3.8:1 in the CST and 4.1:1 in the DAT, although a statistically significant difference between the two was only found in the DAT at this time point (P < 0.05). Finally, we demonstrated that oligodendrocytes, the myelin-forming cells in the central nervous system, constitute at least a portion of the cells undergoing apoptosis within areas of Wallerian degeneration.     

Methylprednisolone inhibits Nogo-A protein expression after acute spinal cord injury

Oligodendrocyte-produced Nogo-A has been shown to inhibit axonal regeneration. Methylprednisolone plays an effective role in treating spinal cord injury, but the effect of methylprednisolone on Nogo-A in the injured spinal cord remains unknown. The present study established a rat model of acute spinal cord injury by the weight-drop method. Results showed that after injury, the motor behavior ability of rats was reduced and necrotic injury appeared in spinal cord tissues, which was accompanied by increased Nogo-A expression in these tissues. After intravenous injection of high-dose methylprednisolone, although the pathology of spinal cord tissue remained unchanged, Nogo-A expression was reduced, but the level was still higher than normal. These findings implicate that methylprednisolone could inhibit Nogo-A expression, which could be a mechanism by which early high dose methylprednisolone infusion helps preserve spinal cord function after spinal cord injury.