SPINAL-CORD INJURY IN THE RAT - TREATMENT WITH BACTERIAL LIPOPOLYSACCHARIDE AND INDOMETHACIN ENHANCES CELLULAR REPAIR AND LOCOMOTOR FUNCTION
SPINAL-CORD INJURY IN THE RAT - TREATMENT WITH BACTERIAL LIPOPOLYSACCHARIDE AND INDOMETHACIN ENHANCES CELLULAR REPAIR AND LOCOMOTOR FUNCTION
复制标题
DOI：
10.1006/exnr.1994.1043
复制
发表时间：
1994-03-01
影响因子：
5.3
通讯作者：
FITCH, MT
中科院分区：
文献类型：
--
作者：
GUTH, L;ZHANG, ZY;FITCH, MT
大鼠脊髓的创伤导致损伤，其特征是胶质细胞向内生长，巨噬细胞聚集，并逐渐发展为坏死和空化。由于当适当激活时，星形胶质细胞和巨噬细胞都会分泌促进生长的细胞因子，我们研究了刺激这些细胞分泌活动的药物治疗是否可以促进组织修复和减少创伤脊髓的坏死。采用硬膜外挤压大鼠脊髓TS模型，给予(1)脂多糖(LPS)或ImuVert刺激细胞因子分泌；(2)吲哚美辛通过抑制前列腺素合成减少坏死；(3)LPS+吲哚美辛或(Iv)载体。28d后通过光镜图像分析对病变部位进行定量检查。对照组动物的损伤表现为巨大的空洞，大量充满碎片的巨噬细胞的渗透，相对较少的轴突。用内毒素或ImuVert治疗可显著降低空化程度，增加病变内细胞和轴突的数量。内毒素+消炎痛治疗明显优于单纯内毒素治疗，而单纯消炎痛治疗无效。为了检验治疗组和对照组大鼠之间的组织病理学差异是否可能反映在功能改善上，造成大鼠挫伤(体重下降)，并在术后28天用Tarlov评分对其步行能力进行量化。脂多糖+吲哚美辛治疗可显著改善中度(1.25g×20 cm)损伤动物的运动功能。我们的结论是，脊髓损伤后的组织修复和功能恢复通过联合治疗促进非神经细胞的分泌活动和抑制前列腺素合成的药物来促进。这些结果表明，寻找更有效的治疗方法应该包括对具有不同药理特异性的药物组合的研究。(C)1994年学术出版社。
Trauma to the rat's spinal cord results in a lesion characterized by ingrowth of glial cells, accumulation of macrophages, and the progressive development of necrosis and cavitation. Since, when appropriately activated, both astrocytes and macrophages secrete growth-promoting cytokines, we examined whether treatment with drugs that stimulate the secretory activities of these cells might promote tissue repair and reduce necrosis in the traumatized spinal cord. The spinal cord of rats was crushed extradurally at TS and the rats were injected intraperitoneally with (i) a lipopolysaccharide (LPS) or ImuVert to activate cytokine secretion, (ii) Indomethacin to reduce necrosis by inhibiting prostaglandin synthesis, (iii) a combination of LPS+Indomethacin, or (iv) vehicle. After 28 days the lesion site was examined quantitatively by light microscopical image analysis. The lesion of vehicle-treated control animals showed large cavities, extensive infiltration by debris-engorged macrophages, and relatively few axons. Treatment with LPS or ImuVert significantly reduced the degree of cavitation and increased the number of cells and axons in the lesion. Treatment with LPS+Indomethacin was significantly more effective than treatment with LPS alone, while treatment with Indomethacin alone was ineffective. To test whether the histopathological differences between treated and control rats might be reflected in functional improvement, rats were subjected to a contusion (weight-drop) injury and their walking ability was quantified by the Tarlov scale for 28 days postoperatively. Treatment with LPS+Indomethacin significantly improved locomotor function of animals subjected to a moderate (1.25 g x 20 cm) injury. We conclude that tissue repair and functional recovery after spinal cord injury are enhanced by combined treatment with agents that promote the secretory activities of the nonneuronal cells and that inhibit prostaglandin synthesis. These results indicate that the search for more effective treatments should include studies on combinations of drugs having different pharmacological specificities. (C) 1994 Academic Press, Inc.