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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., (Copyright © 2016. Published by Elsevier B.V.)

To investigate factors that influence the degree of neural regeneration and recovery, we studied 2 olfactory nerve injury models. Transection of the olfactory nerves along the surface of the olfactory bulb was performed in OMP-tau-lacZ mice using either a flexible Teflon blade (mild injury) or a stainless steel blade (severe injury). Histological assessment of recovery within the olfactory bulb was made at 5, 14, and 42 days after injury. We used X-gal staining to label the degenerating and regenerating olfactory nerve fibers and immunohistochemical staining to detect the presence of reactive astrocytes and macrophages. Areas of injury-associated tissue were significantly smaller in the mild injury model, and at 42 days, the regenerated nerves had reestablished connections to the glomerular layer of the bulb. With severe injury, there were larger areas of injury-associated tissue, more astrocytes and macrophages, and a decrease in regenerated nerve fibers. When dexamethasone (DXM) was injected after severe injury, there was a significant reduction in injury-associated tissue, better nerve recovery, and fewer astrocytes and macrophages. These results demonstrate that recovery in the olfactory system varies with the severity of injury and that DXM treatment may have therapeutic value by reducing injury-associated tissue and improving recovery outcome.

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. [ABSTRACT FROM AUTHOR]

We previously reported that treatment with an anti-inflammatory drug, specifically a steroid, is effective in improving recovery during the acute phase of head injury. Clinically, however, patients with head injury usually become aware of their olfactory loss several weeks or months after the injury, which may be a critical factor in poor recovery from olfactory dysfunction. This raises an important question: When should steroid administration begin in order to achieve optimum improvement of olfactory dysfunction? The present study was designed to reveal the time limit for starting anti-inflammatory treatment for better improvement of post-traumatic olfactory dysfunction. Olfactory nerve transection (NTx) was performed in olfactory marker protein (OMP)-tau-lacZ mice and subcutaneous injections of dexamethasone sodium phosphate for 5 consecutive days was started at 7, 14, 28, and 42 days after the NTx (7-, 14-, 28-, and 42-day time-points). Histological assessment of olfactory nerve recovery in the olfactory bulb was made at 5, 14, and 42 days after the start of drug treatment. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential testing also were performed. Animals treated at 7 days post-injury had less injury-associated tissue with fewer astrocytes and macrophages and better histological and functional nerve recovery, compared with control mice. However, those treated at 14, 28, or 42 days post-injury did not show significant histological or functional differences between saline control and treatment groups. These findings suggest that an anti-inflammatory treatment using steroids for traumatic olfactory dysfunction may be effective if started at least by 7 days, but may be ineffective at 14 days or later after head injury. [ABSTRACT FROM AUTHOR]

Highlights: [•] Anti-IL-6R antibody decreased astrocytes and macrophages in damaged olfactory bulbs. [•] Anti-IL-6R antibody contributes to olfactory nerve regeneration morphologically. [•] Anti-IL-6R antibody contributes to functional recovery of the olfactory system. [•] Blockade of IL-6R could be a new treatment for traumatic olfactory dysfunction. [Copyright &y& Elsevier]

A new olfactory test, the odor stick identification test for Japanese (OSIT-J), has been developed in Japan. To determine if the OSIT-J would be effective cross-culturally, we administered the test to 52 US and 50 Japanese subjects reporting normal olfactory function. The average composite OSIT-J test score for US subjects was significantly lower (77%) than that for Japanese subjects (94%, P < 0.0001). Both US and Japanese subjects correctly identified eight of the 13 odorants included in the OSIT-J with scores of 80% or higher. However, for five odorants, the US subjects' scores fell below 80% and were consistently lower than Japanese subjects, presumably reflecting cultural differences in odor experience. Most of the US subjects found the OSIT-J to be easy, interesting, pleasant, and short in duration. Although the 13-odorant OSIT-J was found to be suitable for testing US populations, elimination of five test odorants that were unfamiliar to US subjects significantly enhanced the test's effectiveness. Findings from this study emphasize the importance of identifying test odorants that may have a cultural bias, a crucial issue when comparing data obtained from different smell tests used at smell and taste centers around the world. [ABSTRACT FROM AUTHOR]