Changes in TNFα, NFκB and MnSOD protein in the vestibular nuclei after unilateral vestibular deafferentation

摘要

Background Unilateral vestibular deafferentation results in strong microglial and astroglial activation in the vestibular nuclei (VN) that could be due to an inflammatory response. This study was aimed at determining if markers of inflammation are upregulated in the VN after chemical unilateral labyrinthectomy (UL) in the rat, and if the inflammatory response, if any, induces the expression of neuroprotective factors that could promote the plasticity mechanisms involved in the vestibular compensation process. The expressions of inflammatory and neuroprotective factors after chemical or mechanical UL were also compared to verify that the inflammatory response was not due to the toxicity of sodium arsanilate. Methods Immunohistological investigations combined the labeling of tumor necrosis factor α (TNFα), as a marker of the VN inflammatory response, and of nuclear transcription factor κB (NFκB) and manganese superoxide dismutase (MnSOD), as markers of neuroprotection that could be expressed in the VN because of inflammation. Immunoreactivity (Ir) of the VN cells was quantified in the VN complex of rats. Behavioral investigations were performed to assess the functional recovery process, including both static (support surface) and dynamic (air-righting and landing reflexes) postural tests. Results Chemical UL (arsanilate transtympanic injection) induced a significant increase in the number of TNFα-Ir cells in the medial and inferior VN on both sides. These changes were detectable as early as 4 h after vestibular lesion, persisted at 1 day, and regained nearly normal values at 3 days. The early increase in TNFα expression was followed by a slightly delayed upregulation of NFκB 8 h after chemical UL, peaking at 1 day, and regaining control values 3 days later. By contrast, upregulation of MnSOD was more strongly delayed (1 day), with a peak at 3 days, and a return to control values at 15 days. Similar changes of TNFα, NFκB, and MnSOD expression were found in rats submitted to mechanical UL. Behavioral observations showed strong posturo-locomotor deficits early after chemical UL (1 day) and a complete functional recovery 6 weeks later. Conclusions Our results suggest that the upregulation of inflammatory and neuroprotective factors after vestibular deafferentation in the VN may constitute a favorable neuronal environment for the vestibular compensation process.