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大剂量 IgG 抑制局部炎症,促进嗅觉系统损伤后的功能恢复。

High-dose IgG suppresses local inflammation and facilitates functional recovery after olfactory system injury.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

出版信息

Ann Clin Transl Neurol. 2022 Jun;9(6):770-777. doi: 10.1002/acn3.51554. Epub 2022 May 19.

DOI:10.1002/acn3.51554
PMID:35588199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9186131/
Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

INTERPRETATION

These findings suggest that high-dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/32346e68a9c7/ACN3-9-770-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/74d0d6c389df/ACN3-9-770-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/b94f326716c4/ACN3-9-770-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/32346e68a9c7/ACN3-9-770-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/74d0d6c389df/ACN3-9-770-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/b94f326716c4/ACN3-9-770-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb8/9186131/32346e68a9c7/ACN3-9-770-g001.jpg

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本文引用的文献

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High-Dose Intravenous Immunoglobulin in Skin Autoimmune Disease.大剂量静脉注射免疫球蛋白治疗皮肤自身免疫性疾病。
Front Immunol. 2019 Jun 11;10:1090. doi: 10.3389/fimmu.2019.01090. eCollection 2019.
2
Anti-high mobility group box 1 antibody suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury.抗高迁移率族蛋白 B1 抗体抑制损伤后局部炎症反应,促进嗅神经恢复。
J Neuroinflammation. 2018 Apr 26;15(1):124. doi: 10.1186/s12974-018-1168-7.
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Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury.
静脉注射免疫球蛋白在急性脑损伤中的治疗潜力
Front Immunol. 2017 Jul 31;8:875. doi: 10.3389/fimmu.2017.00875. eCollection 2017.
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Tumor necrosis factor-α antagonist suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury.肿瘤坏死因子-α拮抗剂可抑制局部炎症反应,并促进损伤后嗅神经的恢复。
Auris Nasus Larynx. 2017 Feb;44(1):70-78. doi: 10.1016/j.anl.2016.05.009. Epub 2016 Jun 11.
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Intravenous immunoglobulin G improves neurobehavioral and histological outcomes after traumatic brain injury in mice.静脉注射免疫球蛋白G可改善小鼠创伤性脑损伤后的神经行为和组织学结果。
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Indian J Dermatol Venereol Leprol. 2013 Jul;79 Suppl 7:S35-46. doi: 10.4103/0378-6323.115526.
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Blockade of interleukin-6 receptor suppresses inflammatory reaction and facilitates functional recovery following olfactory system injury.阻断白细胞介素-6 受体可抑制炎症反应,并促进嗅觉系统损伤后的功能恢复。
Neurosci Res. 2013 Jul;76(3):125-32. doi: 10.1016/j.neures.2013.03.015. Epub 2013 Apr 18.
8
Immunoglobulin G (IgG) attenuates neuroinflammation and improves neurobehavioral recovery after cervical spinal cord injury.免疫球蛋白 G(IgG)可减轻颈髓损伤后的神经炎症反应,促进神经行为学恢复。
J Neuroinflammation. 2012 Sep 21;9:224. doi: 10.1186/1742-2094-9-224.
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HMGB1 in development and diseases of the central nervous system.HMGB1 在中枢神经系统发育和疾病中的作用。
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High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes.高迁移率族蛋白 B1 促进 2 型糖尿病小鼠机械性痛觉过敏和脊髓星形胶质细胞激活。
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