Local Inhibition of Rho Signaling by Cell-Permeable Recombinant Protein BA-210 Prevents Secondary Damage and Promotes Functional Recovery following Acute Spinal Cord Injury
Local Inhibition of Rho Signaling by Cell-Permeable Recombinant Protein BA-210 Prevents Secondary Damage and Promotes Functional Recovery following Acute Spinal Cord Injury
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DOI：
10.1089/neu.2008.0613
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发表时间：
2008-11-01
影响因子：
4.2
通讯作者：
McKerracher, Lisa
中科院分区：
文献类型：
--
作者：
Lord-Fontaine, Stephanie;Yang, Fan;McKerracher, Lisa
脊髓损伤（SCI）导致病变部位的Rho激活。在这里，我们证明了BA-210，一种来自C3转移酶的细胞渗透性融合蛋白，配制在纤维蛋白封闭剂中并局部递送到硬脑膜物质上，扩散到脊髓中并以剂量依赖性方式使Rho失活。用BA-210治疗胸脊髓挫伤的大鼠，增加了病变区域周围的组织保留，并导致运动功能的显着改善。在小鼠中，BA-210在损伤时或延迟24小时进行治疗时改善了功能结果。在大鼠和小鼠中，BA-210治疗耐受性良好。大鼠体重正常增加，BA-210治疗对异常性疼痛的发生没有影响。用BA-210灭活Rho有望治疗SCI患者。
Spinal cord injury (SCI) leads to robust Rho activation at the lesion site. Here, we demonstrate that BA-210, a cell-permeable fusion protein derived from C3 transferase, formulated in fibrin sealant and delivered topically onto the dura matter, diffuses into the spinal cord and inactivates Rho in a dose-dependent manner. Treatment with BA-210 in rats with thoracic spinal cord contusion increased tissue sparing around the lesion area and led to significant improvement of locomotor function. In mice, BA-210 improved functional outcome when treatment was either applied at the time of injury or delayed by 24 h. In both rats and mice, treatment with BA-210 was well tolerated. Rats gained body weight normally, and BA-210 treatment had no impact on the development of allodynia. Inactivating Rho with BA-210 holds promise for treating patients with SCI.