Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
Ann Clin Transl Neurol. 2022 Jun;9(6):770-777. doi: 10.1002/acn3.51554. Epub 2022 May 19.
Head trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti-inflammatory treatment using steroids or anti-cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high-dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury.
Olfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. High-dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X-gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test.
High-dose IgG-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG-injected mice.
These findings suggest that high-dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.
由于嗅神经系统损伤,头部创伤可能是导致难治性嗅觉功能障碍的一个原因。在损伤模型中,使用类固醇或抗细胞因子药物的抗炎治疗被认为有助于中枢和外周神经系统的功能恢复,而人们担心它们会引起不良反应。本研究探讨了高剂量免疫球蛋白 G(IgG)是否可以促进损伤后的嗅觉功能恢复。
在 OMP-tau-lacZ 小鼠中进行嗅神经横断术(NTx)以建立损伤模型。在 NTx 后立即腹腔内注射高剂量 IgG,并在药物注射后 5、14、42 和 100 天对嗅球内的恢复进行组织学评估。X-gal 染色标记退化和再生的嗅神经纤维,免疫组织化学染色检测反应性星形胶质细胞和巨噬细胞/小胶质细胞的存在。使用嗅觉回避行为测试评估嗅觉功能。
高剂量 IgG 注射小鼠的损伤相关组织面积明显较小,星形胶质细胞和巨噬细胞/小胶质细胞较少,再生神经纤维增加。嗅觉回避行为测试显示 IgG 注射小鼠的功能恢复得到改善。
这些发现表明,高剂量 IgG 可能为治疗头部损伤后嗅觉功能障碍提供一种新的治疗策略。