Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Gazzi, Italy.
Expert Opin Ther Targets. 2011 Aug;15(8):943-59. doi: 10.1517/14728222.2011.581231.
Traumatic spinal cord injury (SCI) causes severe and permanent functional deficits, due to the primary mechanical insult, followed by secondary tissue degeneration. The direct damage is followed by a second phase of tissue degeneration, which may take place over a period of weeks or even months, causing neuronal and axonal destruction. A key mediator of this process is an acute and robust inflammatory response, which involves the synthesis and release of chemokines and cytokines, and a coordinated recruitment of circulating leucocytes, as well as microglia, from the CNS parenchyma. The search for a 'cure' for SCI has yet to produce a convincingly efficacious treatment that improves the outcome for patients.
This review explores the experimental studies describing the beneficial effects of PPAR receptor modulators in spinal cord trauma.
Because of safety issues and limited data, PPAR agonists are not yet included in SCI-related treatment strategies. PPAR agonists for specific isoforms (α, β/δ and γ) have demonstrated both anti-inflammatory and immunomodulatory properties. Pharmacological activation of PPAR can be considered as a multi-faceted therapeutic target, due to its anti-inflammatory/antioxidant/anti-excitotoxic/pro-energetic profile, reported in some neurological and inflammatory-related diseases.
外伤性脊髓损伤 (SCI) 由于原发性机械损伤，随后是继发性组织退化，会导致严重且永久性的功能缺陷。直接损伤后会发生第二期组织退化，可能持续数周甚至数月，导致神经元和轴突破坏。这个过程的一个关键介质是急性和强烈的炎症反应，涉及趋化因子和细胞因子的合成和释放，以及循环白细胞以及小胶质细胞从中枢神经系统实质的协调募集。寻找 SCI 的“治愈方法”尚未产生一种令人信服的有效治疗方法来改善患者的预后。
这篇综述探讨了描述过氧化物酶体增殖物激活受体 (PPAR) 受体调节剂在脊髓创伤中的有益作用的实验研究。
由于安全问题和数据有限，PPAR 激动剂尚未纳入与 SCI 相关的治疗策略中。针对特定亚型 (α、β/δ 和 γ) 的 PPAR 激动剂已显示出抗炎和免疫调节特性。由于其在一些神经和炎症相关疾病中的抗炎/抗氧化/抗兴奋毒性/促能谱，PPAR 的药理学激活可被视为一种多方面的治疗靶点。
