Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation
Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation
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DOI：
10.1006/exnr.1999.7184
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发表时间：
1999-11-01
影响因子：
5.3
通讯作者：
Anderson, DK
中科院分区：
文献类型：
--
作者：
Lemons, ML;Howland, DR;Anderson, DK
外在因素似乎导致受伤的成人脊髓缺乏再生。这些外在因素很可能包括一组假定的生长抑制分子，称为硫酸软骨素蛋白聚糖（CSPG）。本研究的目的是确定：（1）脊髓挫伤对 CSPG 的影响；表达，（2）CSPGs是否可以通过外源酶应用在体内降解，以及（3）椎管内移植对CSPGs表达的影响。损伤后 4 天，与正常对照（无手术操作）和仅椎板切除术对照相比，脊髓挫伤后，损伤部位及其附近的软骨素 6-硫酸盐蛋白聚糖免疫反应性 (CSPG-IR) 显着增加。损伤后至少 40 天，CSPG-IR 的急剧增加持续存在于病变周围和脊髓背侧二分之一至三分之二处。胶质原纤维酸性蛋白 (GFAP)-IR 模式与 CSPG-IR 模式类似，强化且空间受限。这些结果表明：(1) CSPG 可能导致脊髓损伤后再生缺乏，(2) 星形胶质细胞可能导致 CSPG 的产生。此外，我们的结果表明，使用外源软骨素酶 ABC 可以在体内裂解 CSPG。这种裂解的证明可能是直接评估 CSPG 在体内生长抑制中的作用的模型的基础（研究正在进行中），并具有作为促进生长的治疗方法的潜力。有趣的是，胎儿脊髓的椎管内移植物并没有改变由损伤引起的强大的 CSPG-IR 模式。宿主脊髓中的 CSPG 表达谱与时间匹配的仅挫伤动物相似。 GFAP-IR 模式也是如此。此外，胎儿脊髓组织在移植时通常呈 CSPG 阴性，但在移植后 30 天出现强烈的 CSPG 表达。 CSPG 的增加；移植物中的表达与 GFAP-IR 的适度增加配对。 CSPG-IR 模式表明这些分子可能导致椎管内移植后的有限再生。此外，这表明随着移植物内CSPG表达的发展，移植物的生长许可性可能会随着时间的推移而改变。受伤和移植脊髓中的这些相关性支持了 CSPG 在成人脊髓中的假定生长抑制作用。 (C) 1999 年学术出版社。
Extrinsic factors appear to contribute to the lack of regeneration in the injured adult spinal cord. It is likely that these extrinsic factors include at group of putative growth inhibitory molecules known as chondroitin sulfate proteoglycans (CSPGs). The aims of this study were to determine: (1) the consequences of spinal cord contusion injury on CSPG; expression, (2) if CSPGs can be degraded in vivo by exogenous enzyme application, and (3) the effects of intraspinal transplantation on the expression of CSPGs. Chondroitin 6-sulfate proteoglycan immunoreactivity (CSPG-IR) dramatically increased following spinal cord contusion injury both at and adjacent to the injury site compared to normal controls (no surgical procedure) and laminectomy-only controls by 4 days postinjury. The dramatic increase in CSPG-IR persisted around the lesion and in the dorsal one-half to two-thirds of the spinal cord for at least 40 days postinjury. Glial fibrillary acidic protein (GFAP)-IR patterns were similarly intensified and spatially restricted as CSPG-IR patterns. These results suggest that: (1) CSPGs may contribute to the lack of regeneration following spinal cord injury and (2) astrocytes may contribute to the production: of CSPGs. In addition, our results show that CSPGs could be cleaved in vivo with exogenous chondroitinase ABC application. This demonstration of cleavage may the basis for a model to directly assess CSPGs' role in growth inhibition in vivo (studies in progress) and hold potential as a therapeutic approach to enhance growth. Interestingly, the robust, injury-induced CSPG-IR patterns were not altered by intraspinal grafts of fetal spinal cord. The CSPG expression profile in the host spinal cord was similar to time-matched contusion-only animals. This was also true of GFAP-IR patterns. Furthermore, the fetal spinal cord tissue, which was generally CSPG negative at the time of transplantation, developed robust CSPG expression by 30 days posttransplantation. This increase in CSPG; expression in the graft was paired with a moderate increase in GFAP-IR. CSPG-IR patterns suggest that these molecules may contribute to the limited regeneration seen following intraspinal transplantation. In addition, it suggests that the growth permissiveness of the graft may change overtime as CSPG expression develops within the graft. These correlations in the injured and transplanted spinal cord support CSPGs' putative growth inhibitory effect in the adult spinal cord. (C) 1999 Academic Press.