Docagne Fabian, Muñetón Vilma, Clemente Diego, Ali Carine, Loría Frida, Correa Fernando, Hernangómez Míriam, Mestre Leyre, Vivien Denis, Guaza Carmen
Grupo de Neuroinmunología - Instituto Ramón y Cajal, CSIC -Avda Dr Arce, 37 - 28002 Madrid, Spain.
Mol Cell Neurosci. 2007 Apr;34(4):551-61. doi: 10.1016/j.mcn.2006.12.005. Epub 2007 Jan 16.
Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids.
炎症、自身免疫反应、脱髓鞘和轴突损伤被认为参与了多发性硬化症（MS）的发病机制。了解轴突损伤是导致脱髓鞘还是由脱髓鞘引发是一个关键问题。兴奋性毒性过程可能是白质和轴突损伤的原因。实验和临床研究表明，大麻素可能被证明对治疗MS有效。我们在此使用小鼠MS慢性模型表明，AMPA拮抗剂NBQX可减轻脊髓中的临床症状和轴突损伤。在该模型中，合成大麻素HU210改善症状的同时也伴随着轴突损伤的减少。此外，HU210通过CB1和CB2大麻素受体的必然激活，在体内和体外均降低了AMPA诱导的兴奋性毒性。这些数据共同强调了兴奋性毒性过程在诸如MS等脱髓鞘疾病中的作用以及大麻素的潜在治疗特性。
