The ephrins and Eph receptors make up two large families of bi-directional signaling molecules that are known to play a role in the development of the nervous system. Recently, expression of EphA4 in the developing cochlea was shown, with strong expression in cells lining the osseous spiral lamina (OSL) through which afferent dendrites must pass to reach the organ of Corti (OC). It was also demonstrated that ephrin-B2 and -B3, both of which are known to interact with EphA4, are expressed by spiral ganglion (SG) neurons. To investigate the functional role of EphA4 in the development of inner ear neurons, neonatal rat SG explants were cultured for 72 hours on uniformly coated surfaces or near stripes of EphA4/IgG-Fc-chimera. Control explants were cultured on or near IgG-Fc and EphA1/IgG-Fc-chimera. To assess the roles of ephrin-B2 and -B3 in EphA4 signaling, SG explants were cultured with or without anti-ephrin-B2 and/or -B3 blocking antibodies. Growth patterns of SG neurites at the border of EphA4 receptor stripes showed repulsion, characterized by turning, stopping and/or reversal. In the case of IgG-Fc and EphA1, the neurites grew straight onto the stripes. Treatment with either anti-ephrin-B2 or -B3 blocking antibodies significantly reduced the repulsive effect of an EphA4 stripe. Moreover, when both antibodies were used together, neurites crossed onto EphA4 stripes with no evidence of repulsion. The results suggest that EphA4 provides repulsive signals to SG neurites in the developing cochlea, and that ephrin-B2 and -B3 together mediate this response.
The study was performed to identify the incidence and histology of rare tumors with growth restricted to the internal auditory canal (IAC) that are different from vestibular schwannoma (VS). Furthermore, the question was addressed whether a preoperative diagnosis would be possible in these cases. A series of 351 patients that were operated on for IAC tumors through a transtemporal or translabyrinthine approach was investigated retrospectively. Cases with a tumor entity other than VS were analyzed for symptoms, radiological diagnosis, intraoperative findings and postoperative histolopatology to determine if a differential diagnosis to the common VS can be established prior to surgery. In 15 out of 351 cases (4.3%), uncommon processes of the IAC were determined by histology (6 lipomas, 3 hemangiomas, 2 neurofibromas, 2 menigiomas, 1 facial neuroma and 1 case of bilateral malignant lymphoma). The symptoms and the clinical manifestations were typical for patients with VS so that a preoperative differential diagnosis was not possible in the majority of cases. An analysis of the operation reports revealed that in 10 out of the 15 cases the surgeon suspected an unusual tumor of the IAC during surgery. The results of the present investigation suggest that rare lesions of the IAC can be expected in less than 5% of the cases and that preoperative diagnosis of rare IAC tumors is difficult. Intraoperative findings such as adhesion to cranial nerves and consistency of the tumor often indicate unusual processes, but histological analysis of the removed tissue is essential for the definite diagnosis.
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