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

Abstract

OBJECTIVE:

Olfactory dysfunction is a common finding in head trauma due to injury to the olfactory nerve. We previously reported that anti-inflammatory treatment with steroids improves recovery outcome in olfactory nerve injury models. Clinically, however, steroid administration is not recommended in the acute phase of head injury cases because of concerns regarding its side effects. Tumor necrosis factor (TNF-α) is known to play a key role in inflammatory response to injury. The present study examines if the inhibition of TNF-α can facilitate functional recovery in the olfactory system following injury.

MATERIALS AND METHODS:

Olfactory nerve transection (NTx) was performed in olfactory marker protein (OMP-tau-lacZ) mice to establish injury models. We measured TNF-α gene expression in the olfactory bulb using semi-quantitative and real time polymerase chain reaction (PCR) assays and found that they increase within hours after NTx injury. A TNF-α antagonist (etanercept) was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5-70 days. 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.

RESULTS:

Etanercept-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in etanercept-injected animals.

CONCLUSION:

These findings suggest that inhibition of TNF-α could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

• Authors: Mohammed Omar Al Salihi, Masayoshi Kobayashi, Kengo Tamari, Tomotaka Miyamura, Kazuhiko Takeuchi
• Journal: Auris, nasus, larynx (Auris Nasus Larynx) Vol. 44 Issue 1 Pg. 70-78 (Feb 2017) ISSN: 1879-1476 [Electronic] Netherlands
• PMID: 27297522 (Publication Type: Journal Article)
• Copyright: Copyright © 2016. Published by Elsevier B.V.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Olfactory Marker Protein
• Omp protein, mouse
• Tumor Necrosis Factor-alpha
• Etanercept

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Astrocytes (drug effects)
• Disease Models, Animal
• Etanercept (pharmacology)
• Female
• Inflammation
• Macrophages (drug effects)
• Male
• Mice
• Mice, Transgenic
• Microglia (drug effects)
• Olfactory Bulb (drug effects, metabolism)
• Olfactory Marker Protein (genetics)
• Olfactory Nerve (drug effects, immunology, pathology)
• Olfactory Nerve Injuries
• Real-Time Polymerase Chain Reaction
• Recovery of Function (drug effects)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, genetics)