Cell Transplantation to Restore Lost Auditory Nerve Function is a Realistic Clinical Opportunity.

Hearing is one of our most important means of communication. Disabling hearing loss (DHL) is a long-standing, unmet problem in medicine, and in many elderly people, it leads to social isolation, depression, and even dementia. Traditionally, major efforts to cure DHL have focused on hair cells (HCs).

'Surface Transplantation' for Nerve Injury and Repair: The Quest for Minimally Invasive Cell Delivery.

Cell transplantation is an ambitious, but arguably realistic, therapy for repair of the nervous system. Cell delivery is a major challenge for clinical translation, especially given the apparently inhibitory astrogliotic environment in degenerated tissue. However, astrogliotic tissue also contains endogenous structural and biochemical cues that can be harnessed for functional repair.

Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration.

Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson's disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation.

Trauma-specific insults to the cochlear nucleus in the rat.

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions.

Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus.

Object: Hearing levels following microsurgical treatment gradually deteriorate in a number of patients treated for vestibular schwannoma (VS), especially in the subacute postoperative stage. The cause of this late-onset deterioration of hearing is not completely understood. The aim of this study was to investigate the possibility that reactive gliosis is a contributory factor.

Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by mechanical compression.

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression.

An animal experimental model of auditory neuropathy induced in rats by auditory nerve compression.

Several animal models of auditory neuropathy (AN) have been produced by employing pharmacological agents to damage auditory neurons or hair cells selectively. The specificity of pharmacological lesions is generally assessed by observation of visible structural damage but it is difficult to localize the delivery, which could lead to functional side effects in other anatomical structures. Although genetic analyses of human AN patients have provided important information on the pathophysiology of AN, specific genetic defects have not been fully correlated with functional deficits in the auditory nervous system.

"Replacement of diseased auditory neurons by cell transplantation".

The auditory nerve is an important target in hearing restoration research along with the hair cells. Although there are several potentially useful therapeutic options to rebuild lost hearing, cell transplantation is a very realistic option. Cells can be infused into the auditory nerve without compromising the auditory brainstem responses and damaging the membranous labyrinth.

Vertigo as the sole presenting symptom of cerebellopontine angle meningioma.

We report a rare case of cerebellopontine angle (CPA) meningioma whose sole symptom was severe vertigo. A 39-year-old woman with right CPA meningioma was referred for surgery. She experienced severe vertigo for 2 years without any other symptoms.

Transplantation of conditionally immortal auditory neuroblasts to the auditory nerve.

Cell transplantation is a realistic potential therapy for replacement of auditory sensory neurons and could benefit patients with cochlear implants or acoustic neuropathies. The procedure involves many experimental variables, including the nature and conditioning of donor cells, surgical technique and degree of degeneration in the host tissue. It is essential to control these variables in order to develop cell transplantation techniques effectively.

Rebuilding lost hearing using cell transplantation.

Objective: The peripheral auditory nervous system (cochlea and auditory nerve) has a complex anatomy, and it has traditionally been thought that once the sensorineural structures are damaged, restoration of hearing is impossible. In the past decade, however, the potential to restore lost hearing has been intensively investigated using molecular and cell biological techniques, and we can now part with such a pessimistic view. In this review, we examine an important field in hearing restoration research: cell transplantation.

Cell transplantation to the auditory nerve and cochlear duct.

We have developed a technique to deliver cells to the inner ear without injuring the membranes that seal the endolymphatic and perilymphatic chambers. The integrity of these membranes is essential for normal hearing, and the technique should significantly reduce surgical trauma during cell transplantation. Embryonic stem cells transplanted at the internal auditory meatal portion of an atrophic auditory nerve migrated extensively along it.

Macrophage colony stimulating factor (M-CSF) protects spiral ganglion neurons following auditory nerve injury: morphological and functional evidence.

Because hearing disturbance due to auditory nerve dysfunction imposes a formidable burden on human beings, intense efforts have been expended in experimental and clinical studies to discover ways to restore normal hearing. However, the great majority of these investigations have focused on the peripheral process side of bipolar auditory neurons, and very few trials have focused on ways to halt degenerative processes in auditory neurons from the central process side (in the cerebellopontine angle). In the present study, we investigated whether administration of macrophage colony-stimulating factor (M-CSF) could protect auditory neurons in a rat model of nerve injury.

Apoptosis of auditory neurons following central process injury.

Although apoptotic changes in auditory neurons induced by injury to peripheral processes (dendrites) have been intensively studied, apoptotic changes in auditory neurons induced by injury to central processes (axons of spiral ganglion cells, SGCs) have not been reported previously, probably due to lack of an experimental model. The present study reports for the first time the appearance, extent, and time course of SGC apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine (CP) angle cistern with intraoperative recordings of auditory nerve compound action potentials (CAPs) to ensure highly reproducible results.

Effect of topically applied basic fibroblast growth factor on injured cochlear nerve.

Objective: Trauma-induced hearing loss after cerebellopontine angle manipulation has been regarded as having a hopeless natural course once it occurs. To challenge such a pessimistic view, we investigated whether pharmacological interventions with basic fibroblast growth factor (bFGF) could ameliorate trauma-induced cochlear nerve degeneration.

Methods: The cerebellopontine angle portion of the cochlear nerve of rats was quantitatively compressed, and bFGF was topically administered for 2 weeks with a bFGF-soaked absorbable sponge and an osmotic minipump.

Nimodipine ameliorates trauma-induced cochlear neuronal death.

Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)-activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration.

Temporal pattern of cochlear nerve degeneration following compression injury: a quantitative experimental observation.

Object: It has been empirically recognized that the cochlear nerve is highly vulnerable to traumatic stress resulting from surgical procedures; therefore, careful manipulation of the cochlear nerve is mandatory in preventing trauma-induced hearing loss during cerebellopontine angle (CPA) surgery. There is, however, no precise knowledge about the temporal pattern of cochlear nerve degeneration following trauma. This study was performed to determine the temporal pattern of injury that occurs after cochlear nerve trauma, knowledge of which is indispensable not only to neurosurgeons but also to all those who manage lesions involving the cochlear nerve.

Axonal injury in auditory nerve observed in reversible latency changes of brainstem auditory evoked potentials (BAEP) during cerebellopontine angle manipulations in rats.

Intraoperative monitoring of brainstem auditory evoked potentials (BAEP) has been widely utilized to reduce the incidence of postoperative hearing disturbance due to cerebellopontine angle manipulations. The prolongation of wave V of BAEP is usually used as a criterion to warn the surgeons to modify their surgical maneuvers. However, it is not known whether all neuropathological changes are avoided if BAEP latency intraoperatively returns to the baseline level or some neuropathological changes 'silently' occur even if BAEP normalizes.