Lesional expression of RhoA and RhoB following traumatic brain injury in humans
Lesional expression of RhoA and RhoB following traumatic brain injury in humans
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DOI：
10.1089/0897715041269597
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发表时间：
2004-06-01
影响因子：
4.2
通讯作者：
Schwab, JM
中科院分区：
文献类型：
--
作者：
Brabeck, C;Beschorner, R;Schwab, JM
抑制小GTdR Rho或其下游靶点Rho相关激酶（ROCK）已被证明可促进轴突再生并改善成年大鼠创伤性CNS损伤后的功能恢复。为了确定人类创伤性脑损伤（TBI）后RhoA和RhoB的表达模式，并评估Rho是否是人类药物干预的可能靶点，我们研究了25名闭合性脑损伤后死亡患者的脑标本中RhoA和RhoB的表达模式。通过免疫组织化学方法与来自四名神经病理学未受影响的对照患者的脑组织进行比较。在创伤事件后几小时开始观察到RhoA和RhoB的高度显著的病变上调，并在TBI后持续数月。两种分子的细胞来源包括多形核粒细胞、单核细胞/巨噬细胞和反应性星形胶质细胞。此外，RhoA的表达也被检测到在神经元细胞中的一些情况下。从我们的数据中，我们得出结论，Rho的抑制是一个有前途的机制，为发展新的药理学干预人类TBI。由于观察到的RhoA和RhoB的上调在TBI后几个月仍然是可检测的，我们推测甚至延迟用Rho抑制剂治疗也可能是一种治疗选择。
Inhibition of the small GTPase Rho or of its downstream target Rho-associated kinase (ROCK) has been shown to promote axon regeneration and to improve functional recovery following traumatic CNS lesions in the adult rat. In order to determine the expression pattern of RhoA and RhoB following human traumatic brain injury (TBI) and to assess whether Rho is a possible target for pharmacological intervention in humans, we investigated expression patterns of RhoA and RhoB in brain specimens from 25 patients who died after closed TBI in comparison to brain tissue derived from four neuropathologically unaffected control patients by immunohistochemistry. A highly significant lesional upregulation of both RhoA and RhoB was observed beginning several hours after the traumatic event and continuing for months after TBI. The cellular sources of both molecules included polymorphonuclear granulocytes, monocytes/macrophages, and reactive astrocytes. Additionally, expression of RhoA was also detected in neuronal cells in some of the cases. From our data, we conclude that inhibition of Rho is a promising mechanism for the development of new pharmacological interventions in human TBI. As the observed upregulation of RhoA and RhoB was still detectable months after TBI, we speculate that even delayed treatment with Rho inhibitors might be a therapeutic option.