Ohmura Kazufumi, Kinoshita Takamasa, Tomita Hiroyuki, Okada Hideshi, Shimizu Masayoshi, Mori Kosuke, Taniguchi Toshiaki, Suzuki Akio, Iwama Toru, Hara Akira
Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of Neurosurgery, Ogaki Tokusyukai Hospital, Gifu, Japan.
Biochem Biophys Res Commun. 2024 Jan 8;691:149286. doi: 10.1016/j.bbrc.2023.149286. Epub 2023 Nov 21.
Vincristine-induced peripheral neuropathy (VIPN) adversely affects the quality of life and treatment continuity of patients. The endothelial glycocalyx (eGCX) protects nerves from harmful substances released from the capillary vessels, but its role in peripheral neuropathy remains unclear. We investigated the impact of eGCX protection on VIPN. Using a murine model of VIPN, we administered nafamostat mesylate to protect the eGCX shedding, and analyzed the eGCX integrity and manifestation of peripheral neuropathy. Nafamostat treatment suppressed allodynia associated with neuropathy. Additionally, nafamostat administration resulted in the suppression of increased vascular permeability in capillaries of peripheral nerves, further indicating its positive influence on eGCX in VIPN model mice. This study provided the importance of eGCX in VIPN. With the potential for rapid clinical translation through drug repositioning, nafamostat may be a new promising treatment for the prevention of VIPN.
长春新碱诱导的周围神经病变（VIPN）会对患者的生活质量和治疗连续性产生不利影响。内皮糖萼（eGCX）可保护神经免受毛细血管释放的有害物质的侵害，但其在周围神经病变中的作用仍不清楚。我们研究了eGCX保护对VIPN的影响。利用VIPN小鼠模型，我们给予甲磺酸萘莫司他以保护eGCX脱落，并分析了eGCX完整性和周围神经病变的表现。萘莫司他治疗可抑制与神经病变相关的异常性疼痛。此外，给予萘莫司他可抑制周围神经毛细血管中血管通透性的增加，进一步表明其对VIPN模型小鼠的eGCX有积极影响。本研究证明了eGCX在VIPN中的重要性。由于通过药物重新定位有快速临床转化的潜力，萘莫司他可能是预防VIPN的一种新的有前景的治疗方法。
