A Time Limit for Initiating Anti-Inflammatory Treatment for Improved Olfactory Function after Head Injury

Masayoshi Kobayashi, Kengo Tamari, Masako Kitano, Kazuhiko Takeuchi

We previously reported that treatment with an anti-inflammatory drug, specifically a steroid, is effective in improving recovery outcome during 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 OMP (olfactory marker protein)-tau-lacZ mice and subcutaneous injections of dexamethasone sodium phosphate (DXM) 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 were also 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 to 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.