The ability of resident cells to induce apoptosis of invading immune cells is a major regulatory factor operating in immune-privileged tissues, including the nervous system. We investigated the cellular and molecular factors participating in modulation of immune response in peripheral nerves, focusing on two cytotoxic pathways: fas ligand (fasL) and perforin. fasL and perforin expression was found by immunochemistry on Schwann cells (Sc) in nerve biopsies from patients with chronic inflammatory demyelinating polyneuritis and on human Sc cultures. Treatment of Sc with tumor necrosis factor (TNF) alpha and interferon (IFN) gamma upregulated the expression of both molecules. In a coculture model, Sc exposed to TNFalpha or IFN gamma were able to induce both apoptotic and lytic injury of T-lymphocytes. Inactivation of fasL with the neutralizing antibody NOK-2 abolished T-cell apoptosis induced by Sc treated with TNFalpha, but not by Sc treated with IFN gamma. Conversely, T-cell lysis was significantly decreased when IFN gamma-activated Sc were treated with concanamycin A, which inhibited perforin release. At variance with T-lymphocytes, B-cells were less sensitive to cytokine-treated Sc toxicity. Thus, Sc exposed to inflammatory cytokines have the capacity of inducing selective damage of T-lymphocytes and have the potential of regulating the immune response in the peripheral nervous system.
Objective Vestibular schwannoma (VS) is a benign tumor of the lateral skull base. Different microscopic surgical techniques are described in literature: the retrosigmoid and translabyrinthine approaches are used to treat big tumors located in the cerebellopontine angle, and the middle cranial fossa approach is utilized for small tumors with good hearing preservation. The expanded transcanal transpromontorial (ExpTT) approach is a combined microscopic-endoscopic technique previously indicated for Koos stage I and II VS and now proposed for larger VS, up to 3 cm in diameter, with linear progression into the cerebellopontine angle and touching the brainstem. Study Design The study was a retrospective case series of patients who underwent ExpTT surgery for VS in our ear, nose, and throat department. Setting We reviewed the surgical videos and electrophysiologic data recorded during the surgical operations. Subjects and Methods From January 2015 to January 2017, 20 patients affected by Koos stage II and III VS underwent surgery in our department with the ExpTT approach. This novel technique is described step by step, with a focus on the surgical procedure and anatomic landmarks; outcomes are detailed in terms of early and late complications. The mean follow-up was 15 months. Results The ExpTT approach permitted, in all patients, gross total resection of the tumor without any complication and with preservation of facial nerve function. All patients had a good postoperative recovery. Conclusion The ExpTT technique is a new approach that combines the advantages of a microscopic technique with the ones offered by the endoscope in removal of VS.
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