Browsing by Subject "Facial nerve"

Now showing 1 - 3 of 3
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    Cellular Sources and Neuroprotective Roles of Interleukin-10 in the Facial Motor Nucleus after Axotomy
    (MDPI, 2022-10-09) Runge, Elizabeth M.; Setter, Deborah O.; Iyer, Abhirami K.; Regele, Eric J.; Kennedy, Felicia M.; Sanders, Virginia M.; Jones, Kathryn J.; Anatomy, Cell Biology and Physiology, School of Medicine
    Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA. Il10 mRNA co-localized with microglia before and after axotomy, but microglial production of IL-10 protein was not detected. To determine whether any single source of IL-10 was critical for FMN survival, Cre/Lox mouse strains were utilized to selectively knock out IL-10 in neurons, astrocytes, and microglia. In agreement with the localization data reflecting concerted IL-10 production by multiple cell types, no single cellular source of IL-10 alone could provide neuroprotection after FNA. These findings suggest that coordinated neuronal and astrocytic IL-10 production is necessary for FMN survival and has roles in neuronal homeostasis, as well as neuroprotective trophism after axotomy.
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    Facial Nerve Sacrifice During Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma
    (Sage, 2021-02-25) Yesensky, Jessica; Solis, Roberto N.; Bewley, Arnaud; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objective: We analyzed the incidence of facial nerve sacrifice during parotidectomy for metastatic cutaneous squamous cell carcinoma (CSCC). Study design: We retrospectively reviewed the charts of patients with cutaneous squamous cell carcinoma. Setting: We used our CSCC institutional database, which includes patients treated at the University of California-Davis from 2001 to 2018. Methods: We evaluated patients who presented with biopsy-proven head and neck CSCC who underwent parotidectomy as a part of surgical treatment. We assessed the frequency of facial nerve sacrifice required in patients with normal preoperative facial nerve function with metastatic disease to the parotid. We evaluated the association between sacrifice and high-risk tumor variables using multivariate analysis. Results: We identified 53 patients with parotid metastasis and normal preoperative facial nerve function. Thirteen percent of patients required sacrifice of the main trunk of the facial nerve and 27% required sacrifice of a branch of the facial nerve. All patients who underwent facial nerve sacrifice had extracapsular spread (ECS). Perineural invasion (PNI) in the primary tumor (odds ratio [OR], 9.11; P = .041) and location of metastasis within the parotid body (OR, 6.6; P = .044) were independently associated with facial nerve sacrifice. Conclusion: Patients with regionally metastatic CSCC to the parotid gland frequently require sacrifice of all or a component of the facial nerve despite normal preoperative function. The likelihood of nerve sacrifice is highest for tumors with PNI and metastatic disease within the body of the parotid.
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    Immunoregulation of the central response to peripheral nerve injury: motoneuron survival and relevance to ALS
    (2017-04) Setter, Deborah Olmstead; Jones, Kathryn J.; Block, Michelle L.; Sanders, Virginia M.; Sengelaub, Dale R.; Xu, Xiao-Ming
    Facial nerve axotomy (FNA) in immunodeficient mice causes significantly more facial motoneuron (FMN) loss relative to wild type (WT), indicating that the immune system is neuroprotective. Further studies reveal that both CD4+ T cells and interleukin 10 (IL-10) act centrally to promote neuronal survival after injury. This study first investigated the roles of IL-10 and CD4+ T cells in neuroprotection after axotomy. CD4+ T cell-mediated neuroprotection requires centrally-produced IL-10, but the source of IL-10 is unknown. Using FNA on IL-10 reporter mice, immunohistochemistry was employed to identify the IL-10 source. Unexpectedly, axotomy induced astrocyte production of IL-10. To test if microglia- or astrocyte-specific IL-10 is needed for neuroprotection, cell-specific conditional knockout mice were generated. Neither knockout scenario affected FMN survival after FNA, suggesting that coordinated IL-10 production by both glia contributes to neuroprotection. The effect of immune status on the post-FNA molecular response was studied to characterize CD4+ T cell-mediated neuroprotection. In the recombinase-activating gene2 knockout (RAG-2-/-) mouse model of immunodeficiency, glial microenvironment responses were significantly impaired. Reconstitution with CD4+ T cells restored glial activation to normal levels. Motoneuron regeneration responses remained unaffected by immune status. These findings indicate that CD4+ T cell-mediated neuroprotection after injury occurs indirectly via microenvironment regulation. Immunodysregulation is evident in amyotrophic lateral sclerosis (ALS), and FMN survival after FNA is worse in the mutant superoxide dismutase (mSOD1) mouse model of ALS. Further experiments reveal that mSOD1 CD4+ T cells are neuroprotective in RAG-2-/- mice, whereas mSOD1 whole splenocytes (WS) are not. The third aim examined if the mSOD1 WS environment inhibits mSOD1 CD4+ T cell glial regulation after axotomy. Unexpectedly, both treatments were equally effective in promoting glial activation. Instead, mSOD1 WS treatment induced a motoneuron-specific death mechanism prevalent in ALS. In conclusion, the peripheral immune system regulates the central glial microenvironment utilizing IL-10 to promote neuronal survival after axotomy. Astrocytes, specifically, may be responsible for transducing peripheral immune signals into microenvironment regulation. Additionally, the immune system in ALS may directly participate in disease pathology.