Jesse Brown VA Medical Center, University of Illinois, Chicago, USA.
Brain Res. 2010 Nov 11;1360:177-92. doi: 10.1016/j.brainres.2010.09.010. Epub 2010 Sep 15.
Simvastatin and recombinant human erythropoietin (rhEpo) are implicated as potential therapeutic candidates for traumatic brain injury (TBI). Prominent effects of simvastatin include its anti-inflammatory, neurotrophic and neuroregenerative actions studied in various models of neuronal injury. On the other hand, rhEpo has been shown to promote cell survival mechanisms by producing anti-apoptotic and cell proliferative actions. Beneficial effects of rhEpo and statin monotherapies have been well studied. However, there are no reports showing combined use of rhEpo and statins after TBI. This investigation examined if combined efficacy of cell proliferative ability of rhEpo along with the neuroregenerative ability of simvastatin will render maximum recovery in a controlled cortical impact (CCI) mouse model of TBI. Results showed that compared to baseline TBI, rhEpo was more effective than simvastatin in promoting cell proliferation while simvastatin was more effective than rhEpo in restoring axonal damage following TBI. Combined treatment with simvastatin and rhEpo maximally restored axonal integrity while simultaneously inducing greater proliferation of newly formed cells resulting in better functional recovery after TBI than either alone. This is the first study showing the efficacy of erythropoietin-simvastatin combinational therapeutic approach in achieving greater structural and cognitive recovery after TBI.
辛伐他汀和重组人红细胞生成素（rhEpo）被认为是创伤性脑损伤（TBI）的潜在治疗候选药物。辛伐他汀的显著作用包括其在各种神经元损伤模型中研究的抗炎、神经营养和神经再生作用。另一方面，rhEpo 通过产生抗细胞凋亡和细胞增殖作用来促进细胞存活机制。rhEpo 和他汀类药物单一疗法的有益作用已经得到了很好的研究。然而，没有报道显示 TBI 后 rhEpo 和他汀类药物联合使用。这项研究检查了 rhEpo 的细胞增殖能力和辛伐他汀的神经再生能力联合使用是否会在 TBI 的控制性皮质撞击（CCI）小鼠模型中实现最大恢复。结果表明，与 TBI 基线相比，rhEpo 在促进细胞增殖方面比辛伐他汀更有效，而辛伐他汀在 TBI 后恢复轴突损伤方面比 rhEpo 更有效。辛伐他汀和 rhEpo 的联合治疗最大限度地恢复了轴突完整性，同时诱导了更多新形成细胞的增殖，从而在 TBI 后实现了更好的功能恢复，优于单独使用任何一种药物。这是第一项研究表明，rhEpo-辛伐他汀联合治疗方法在实现 TBI 后更大的结构和认知恢复方面的疗效。
