ESS greatly enhances the delivery of nasal solutions, regardless of delivery device. Pressurized spray solutions in un-operated sinuses provide little more than nasal cavity distribution. Use of squeeze bottle/neti pot post-ESS offers a greatly enhanced ability to deliver solutions to the paranasal sinuses.

Murine models are ideal for studying cochlear gene transfer as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, due to its small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAV) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear and allows for near-complete preservation of low and middle frequency hearing. In the present study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6, and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus (CMV) promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells (IHCs) were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

In the present study, glial cell responses to spiral ganglion neuron (SGN) degeneration were evaluated using a murine model of auditory neuropathy. Ouabain, a well-known Na,K-ATPase inhibitor, has been shown to induce SGN degeneration while sparing hair cell function. In addition to selectively removing type I SGNs, ouabain leads to hyperplasia and hypertrophy of glia-like cells in the injured auditory nerves. As the transcription factor Sox2 is predominantly expressed in proliferating and undifferentiated neural precursors during neurogenesis, we sought to examine Sox2 expression patterns following SGN injury by ouabain. Real-time RT-PCR and Western blot analyses of cochlea indicated a significant increase in Sox2 expression by 3 days posttreatment with ouabain. Cells incorporating bromodeoxyuridine (BrdU) and expressing Sox2 were counted in the auditory nerves of control and ouabain-treated ears. The glial phenotype of Sox2 + cells was identified by two neural glial markers: S100 and Sox10. The number of Sox2 + glial cells significantly increased at 3 days post-treatment and reached its maximum level at 7 days post-treatment. Similarly, the number of BrdU + cells increased at 3 and 7 days post-treatment in the injured nerves. Quantitative analysis with dual-immunostaining procedures indicated that about 70% of BrdU + cells in the injured nerves were Sox2 + glial cells. These results demonstrate that up-regulation of Sox2 expression is associated with increased cell proliferation in the auditory nerve after injury.

Patients with spontaneous cerebrospinal fluid otorrhea are often middle-aged and obese, with females being affected nearly twice as often as males. Empty or partially empty sella was observed in 80% of patients with spontaneous cerebrospinal fluid otorrhea as demonstrated by preoperative magnetic resonance imaging. Patients with spontaneous cerebrospinal fluid otorrhea who display these demographic and radiographic features should be further evaluated for the presence of idiopathic intracranial hypertension.

Application of ouabain to the round window membrane of the gerbil selectively induces the death of most spiral ganglion neurons and thus provides an excellent model for investigating the survival and differentiation of embryonic stem cells (ESCs) introduced into the inner ear. In this study, mouse ESCs were pretreated with a neural-induction protocol and transplanted into Rosenthal's canal (RC), perilymph, or endolymph of Mongolian gerbils either 1-3 days (early post-injury transplant group) or 7 days or longer (late post-injury transplant group) after ouabain injury. Overall, ESC survival in RC and perilymphatic spaces was significantly greater in the early post-injury microenvironment as compared to the later post-injury condition. Viable clusters of ESCs within RC and perilymphatic spaces appeared to be associated with neovascularization in the early post-injury group. A small number of ESCs transplanted within RC stained for mature neuronal or glial cell markers. ESCs introduced into perilymph survived in several locations, but most differentiated into glia-like cells. ESCs transplanted into endolymph survived poorly if at all. These experiments demonstrate that there is an optimal time window for engraftment and survival of ESCs that occurs in the early post-injury period.