FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury
FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury
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DOI：
10.1006/exnr.2002.7975
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发表时间：
2002-09-01
影响因子：
5.3
通讯作者：
Springer, J
中科院分区：
文献类型：
--
作者：
Nottingham, S;Knapp, P;Springer, J
本研究的重点是检查FK 506（一种抑制钙调磷酸酶激活的免疫抑制剂）限制脊髓损伤（SCI）后少突胶质细胞中caspase-3激活的能力。为了更好地确定SCI后少突胶质细胞中钙调磷酸酶和半胱天冬酶-3激活的作用，大鼠接受脊髓挫伤，然后用FK 506或雷帕霉素（另一种对钙调磷酸酶激活没有可检测的抑制作用的免疫抑制剂）治疗。然后在损伤后8天处死动物，并使用免疫荧光组织化学处理脊髓组织以检测腹侧和背侧白色物质中的细胞半胱天冬酶-3活化。在所有治疗组中，发现许多少突胶质细胞在损伤中心的近端和远端区域表达活化形式的caspase-3。然而，我们的研究结果表明，FK 506治疗，而不是雷帕霉素减少表达激活的caspase-3的少突胶质细胞的数量，并增加了存活的少突胶质细胞在背侧白色的问题。这些结果提供了初步的证据，即减少钙调磷酸酶和随后的caspase-3激活的作用的药物可能被证明在创伤性SCI的治疗中是有益的。(C)2002 Elsevier Science（美国）。
The focus of this study is to examine the ability of FK506, an immunosuppressant that inhibits calcineurin activation, to limit caspase-3 activation in oligodendroglia following spinal cord injury (SCI). To better establish a role for calcineurin and caspase-3 activation in oligodendroglia following SCI, rats received a contusion injury to the spinal cord followed by treatment with FK506 or rapamycin (another immunosuppressant with no detectable inhibitory action on calcineurin activation). Animals were then sacrificed at 8 days postinjury and spinal cord tissue was processed using immunofluorescence histochemistry to examine cellular caspase-3 activation in ventral and dorsal white matter. In all treatment groups, numerous oligodendroglia were found to express the activated form of caspase-3 in regions proximal and distal to the injury epicenter. However, our findings suggest that treatment with FK506, but not rapamycin reduces the number of oligodendroglia expressing activated caspase-3 and increases the number of surviving oligodendroglia in dorsal white matter. These results provide initial evidence that agents that reduce the actions of calcineurin and subsequent caspase-3 activation may prove beneficial in the treatment of traumatic SCI. (C) 2002 Elsevier Science (USA).