Tumor necrosis factor-α antagonist suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury

Salihi, Mohammed Omar Al; Kobayashi, Masayoshi; Tamari, Kengo; Miyamura, Tomotaka; Takeuchi, Kazuhiko

doi:10.1016/j.anl.2016.05.009

Cited by 17 publications

(26 citation statements)

References 34 publications

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“…We also sought to identify potential deleterious variants associated with disease duration among RA patients. Our pathway analysis focusing on variants enriched among RA patients with disease duration ≥3-year highlighted seven novel genes in olfactory transduction pathway (Table 1 ), which has been previously reported to be implicated in regulating inflammatory responses [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing

et al. 2017

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Rheumatoid arthritis (RA) is a highly prevalent chronic autoimmune disease. However, genetic and environmental factors involved in RA pathogenesis are still remained largely unknown. To identify the genetic causal variants underlying pathogenesis and disease progression of RA patients, we undertook the first comprehensive whole-exome sequencing (WES) study in a total of 124 subjects including 58 RA cases and 66 healthy controls in Han Chinese population. We identified 378 novel genes that were enriched with deleterious variants in RA patients using a gene burden test. The further functional effects of associated genetic genes were classified and assessed, including 21 newly identified genes that were involved in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, focal adhesion and glycerophospholipid metabolism pathways relevant to RA pathogenesis. Moreover, six pathogenic variants were investigated and structural analysis predicted their potentially functional alteration by homology modeling. Importantly, five novel and rare homozygous variants (NCR3LG1, RAP1GAP, CHCHD5, HIPK2 and DIAPH2) were identified, which may exhibit more functional impact on RA pathogenesis. Notably, 7 genes involved in the olfactory transduction pathway were enriched and associated with RA disease progression. Therefore, we performed an efficient and powerful technique WES in Chinese RA patients and identified novel, rare and common disease causing genes that alter innate immunity pathways and contribute to the risk of RA. Findings in this study may provide potential diagnostic tools and therapeutic strategies for RA patients.

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Section: Discussionmentioning

confidence: 99%

Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing

et al. 2017

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“…The advantage of using these mice is that a histological assessment of degenerating and regenerating olfactory nerve fibers can be performed using a standard method for staining and light microscopy. Although the exact function of OMP and effects of lack of OMP has not been revealed yet, many previous studies have shown that OMP-tau-lacZ mice are capable of recovering olfactory function after olfactory nerve injury [ 13 , 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…To determine if olfactory function recovered after the NTx, a smell detection test using avoidance conditioning behavior to cycloheximide was administered to mice before and after the NTx as reported previously [ 13 , 14 ]. Cycloheximide has a peculiar odor and unpleasant taste for mice.…”

Section: Methodsmentioning

confidence: 99%

“…To confirm that regenerated olfactory receptor cell axons were functionally reconnected to the olfactory bulb after the olfactory NTx, field potentials evoked by electrical stimulation of the olfactory mucosa were measured in the olfactory bulb of mice that completed the cycloheximide olfactory function test as reported previously [ 13 , 14 ]. For this group of mice, the NTx procedure was bilateral, resulting in a complete loss of olfactory function.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported using an olfactory nerve injury model in mice that anti-inflammatory treatment with steroids, anti-interleukin-6 (IL-6) receptor antibody, or tumor necrosis factor (TNF)-α blocker, during the acute phase of injury is effective in suppressing the inflammatory reaction and local glial scar formation and improves recovery outcomes after olfactory nerve transection (NTx) [ 12 – 14 ]. In clinical practice, however, these drugs are not typically used for the treatment of head injury patients since several studies reported that steroids do not have a significant efficacy on morbidity and mortality in patients with severe head injury, and there are concerns that steroids may cause serious side effects such as hypertension, hyperglycemia, infection, bone necrosis, and psychosis [ 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Anti-high mobility group box 1 antibody suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury

Kobayashi

Tamari

Salihi

et al. 2018

J Neuroinflammation

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BackgroundRefractory olfactory dysfunction is a common finding in head trauma due to olfactory nerve injury. Anti-inflammatory treatment using steroids is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that steroids can induce side effects. The present study examines if the inhibition of proinflammatory cytokine, high mobility group box 1 (HMGB1), can facilitate olfactory functional recovery following injury.MethodsOlfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. We measured HMGB1 gene expression in the olfactory bulb using semi-quantitative polymerase chain reaction (PCR) assays and examined HMGB1 protein localization in the olfactory bulb using immunohistochemical staining. Anti-HMGB1 antibody 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 OMP in the degenerating and regenerating olfactory nerve fibers, and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using both an olfactory avoidance behavioral test and evoked potential recording.ResultsHMGB1 gene and protein were significantly expressed in the olfactory bulb 12 h after NTx. Anti-HMGB1 antibody-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia and an increase in regenerating nerve fibers. Both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in the anti-HMGB1 antibody-injected mice.ConclusionsThese findings suggest that inhibition of HMGB1 could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

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

Nishida

Kobayashi

Ishigami

et al. 2022

Ann Clin Transl Neurol

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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 IgGinjected 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.

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Tumor necrosis factor-α antagonist suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury

Cited by 17 publications

References 34 publications

Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing

Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing

Anti-high mobility group box 1 antibody suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury

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

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