PDF(Pubmed)
Abstract：
Prolonged infusion of a high dose of kynurenic acid (KYNA) reduces the myelin content in the rat spinal cord with preservation of the axonal integrity and without inducing an inflammatory response. We hypothesized that subdural infusion of a high concentration of KYNA can induce myelin loss in the optic nerves (ONs) of chickens. However, existing methods to deliver agents to the ON are inefficient, unlocalized and provide only acute exposure. Thus, we developed a surgical approach for sustained delivery of KYNA to the chicken ON. In brief, the novel surgical technique, which does not include excision of the extraocular muscles, involves incision of the skin and underlying fascial sheath to access the optic nerve within the muscle cone, implantation of a catheter in the dura of the optic nerve, the other end of which exits the orbit under the skin. The catheter runs under the skin near the lateral canthus, over the ears to the back of the neck, where a second incision is made to both implant the osmotic pump and to attach the catheter to the osmotic pump. India ink was used to confirm prolonged sustained administration to the optic nerves and across the chiasm. This surgical model was used to investigate KYNA\'s effect(s) on myelin loss in the ON. ONs of 7-day old chickens were infused with 50 mM KYNA or phosphate buffered saline (PBS) for seven days. Analysis of KYNA-infused contralateral ON g-ratios and protein levels indicated a reduction in myelin. These findings demonstrate the utility of our surgical approach for sustained delivery of KYNA into the ON and suggest a role for KYNA in modulating CNS myelination.
摘要：
长时间输注高剂量的犬尿烯酸（KYNA）可降低大鼠脊髓中的髓磷脂含量，同时保留轴突完整性，并且不会引起炎症反应。我们假设硬膜下输注高浓度的KYNA可以诱导鸡视神经（ON）的髓磷脂损失。然而,现有的将代理递送到ON的方法效率低下，非局部暴露，仅提供急性暴露。因此，我们开发了一种将KYNA持续递送至鸡ON的手术方法。简而言之,新颖的外科技术，这不包括眼外肌的切除，涉及切开皮肤和下面的筋膜鞘以进入肌肉锥内的视神经，在视神经硬膜植入导管,另一端在皮肤下退出轨道。导管在外侧can附近的皮肤下延伸，从耳朵到脖子后面，其中进行第二切口以植入渗透泵并将导管附接到渗透泵。印度墨水用于确认对视神经和交叉的长期持续给药。该手术模型用于研究KYNA对ON中髓磷脂损失的影响。将7天大的鸡的ON用50mMKYNA或磷酸盐缓冲盐水(PBS)输注7天。对KYNA输注的对侧ONg比率和蛋白质水平的分析表明髓鞘减少。这些发现证明了我们的手术方法用于将KYNA持续递送到ON的实用性，并暗示了KYNA在调节CNS髓鞘形成中的作用。
