Sensory overamplification in layer 5 auditory corticofugal projection neurons following cochlear nerve synaptic damage.

Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a plasticity in L5 auditory cortex (ACtx) neurons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We track daily changes in sound processing using chronic widefield calcium imaging of L5 axon terminals on the dorsal cap of the IC in awake, adult mice. Sound level growth functions at the level of the auditory nerve and corticocollicular axon terminals are both strongly depressed hours after noise-induced damage of cochlear afferent synapses. Corticocollicular response gain rebounded above baseline levels by the following day and remained elevated for several weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus and hyperacusis.

Effect of granulocyte colony-stimulating factor on the cochlear nuclei after creation of a partial nerve lesion: an experimental study in rats.

OBJECTIVE The risk of injury of the cochlear nerve during angle (CPA) surgery is high. Granulocyte colony-stimulating factor (G-CSF) has been found in various experimental models of peripheral and CNS injury to have a neuroprotective effect by inhibiting apoptosis and inflammation. However, to the authors' knowledge, the influence of G-CSF on cochlear nerve regeneration has not been reported. This study investigated the neuroprotective effect of G-CSF after a partial cochlear nerve lesion in rats. METHODS A lesion of the right cochlear nerve in adult male Sprague-Dawley rats was created using a water-jet dissector with a pressure of 8 bar. In the first group (G-CSF-post), G-CSF was administrated on Days 1, 3, and 5 after the surgery. The second group (G-CSF-pre/post) was treated with G-CSF 1 day before and 1, 3, and 5 days after applying the nerve injury. The control group received sodium chloride after nerve injury at the various time points. Brainstem auditory evoked potentials (BAEPs) were measured directly before and after nerve injury and on Days 1 and 7 to evaluate the acoustic function of the cochlear nerve. The animals were sacrificed 1 week after the operation, and their brains were fixed in formalin. Nissl staining of the cochlear nuclei was performed, and histological sections were analyzed with a light microscope and an image-processing program. The numbers of neurons in the cochlear nuclei were assessed. RESULTS The values for Waves 2 and 4 of the BAEPs decreased abruptly in all 3 groups in the direct postoperative measurement. Although the amplitude in the control group did not recover, it increased in both treatment groups. According to 2-way ANOVA, groups treated with G-CSF had a significant increase in BAEP Wave II amplitudes on the right side (p = 0.0401) after the applied cochlear nerve injury. With respect to Wave IV, a trend toward better recovery in the G-CSF groups was found, but this difference did not reach statistical significance. In the histological analysis, higher numbers of neurons were found in the G-CSF groups. In the statistical analysis, the difference in the numbers of neurons between the control and G-CSF-post groups reached significance (p = 0.0086). The difference in the numbers of neurons between the control and G-CSF-pre/post groups and between the G-CSF-post and G-CSF-pre/post groups did not reach statistical significance. CONCLUSIONS The use of G-CSF improved the function of the eighth cranial nerve and protected cochlear nucleus cells from destruction after a controlled partial injury of the nerve. These findings might be relevant for surgery that involves CPA tumors. The use of G-CSF in patients with a lesion in the CPA might improve postoperative outcomes.

Contributions of Mouse and Human Hematopoietic Cells to Remodeling of the Adult Auditory Nerve After Neuron Loss.

The peripheral auditory nerve (AN) carries sound information from sensory hair cells to the brain. The present study investigated the contribution of mouse and human hematopoietic stem cells (HSCs) to cellular diversity in the AN following the destruction of neuron cell bodies, also known as spiral ganglion neurons (SGNs). Exposure of the adult mouse cochlea to ouabain selectively killed type I SGNs and disrupted the blood-labyrinth barrier. This procedure also resulted in the upregulation of genes associated with hematopoietic cell homing and differentiation, and provided an environment conducive to the tissue engraftment of circulating stem/progenitor cells into the AN. Experiments were performed using both a mouse-mouse bone marrow transplantation model and a severely immune-incompetent mouse model transplanted with human CD34+ cord blood cells. Quantitative immunohistochemical analysis of recipient mice demonstrated that ouabain injury promoted an increase in the number of both HSC-derived macrophages and HSC-derived nonmacrophages in the AN. Although rare, a few HSC-derived cells in the injured AN exhibited glial-like qualities. These results suggest that human hematopoietic cells participate in remodeling of the AN after neuron cell body loss and that hematopoietic cells can be an important resource for promoting AN repair/regeneration in the adult inner ear.

Facial and Cochlear Nerve Complications following Microsurgical Resection of Vestibular Schwannomas in a Series of 221 Cases.

BACKGROUND: Despite improvements in microsurgical technique and the use of intraoperative electrophysiological monitoring, the potential for facial and cochlear nerve injury remains a possibility in the resection of vestibular schwannomas (VS). We reviewed a series of 221 cases of VS resected via a retrosigmoid approach at our institution from October 2008 to April 2014 and determined the incidence of postoperative facial and cochlear deficits. MATERIAL AND METHODS: A total of 221 patients - 105 (47.5%) male and 116 (52.5%) female - with a mean age of 46.1 years (range 29-73 years), with VS ≥3 cm (n=183, 82.8%) and <3 cm (n=38, 17.2%) underwent surgical resection via a retrosigmoid approach and were evaluated for postoperative facial and cochlear nerve deficits. RESULTS: Near-total resection (>95% removal) was achieved in 199 cases (90%) and subtotal resection (>90% removal) in 22 cases (10%). At 6 month follow-up, House-Brackmann grades I-III were observed in 183 cases (82.8%), grade IV in 16 cases (7.2%), and grade V in 22 cases (10%). Of the 10 patients that had preoperative functional hearing, 3 (33%) retained hearing postoperatively. Cerebrospinal fluid leakage occurred in 6 patients (2.7%), lower cranial nerve palsies in 9 patients (4.1%), and intracranial hematomas 3 cases (1.4%). CONCLUSIONS: The observed incidence of persistent postoperative nerve deficits is very low. Meticulous microsurgical dissection of and around the facial and cochlear nerves with the aid of intraoperative electrophysiological nerve monitoring in the retrosigmoid approach allows for near-total resection of medium and large VS with the possibility of preservation of facial and cochlear nerve function.

Effect of cochlear nerve electrocautery on the adult cochlear nucleus.

HYPOTHESIS: Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. BACKGROUND: Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. METHODS: The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 µm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. RESULTS: Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. CONCLUSION: Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.

Auditory brainstem implant: electrophysiologic responses and subject perception.

OBJECTIVES: The primary aim of this study was to compare the perceptual sensation produced by bipolar electrical stimulation of auditory brainstem implant (ABI) electrodes with the morphology of electrically evoked responses elicited by the same bipolar stimulus in the same unanesthetized, postsurgical state. Secondary aims were to (1) examine the relationships between sensations elicited by the bipolar stimulation used for evoked potential recording and the sensations elicited by the monopolar pulse-train stimulation used by the implant processor, and (2) examine the relationships between evoked potential morphology (elicited by bipolar stimulation) to the sensations elicited by monopolar stimulation. DESIGN: Electrically evoked early-latency and middle-latency responses to bipolar, biphasic low-rate pulses were recorded postoperatively in four adults with ABIs. Before recording, the perceptual sensations elicited by these bipolar stimuli were obtained and categorized as (1) auditory sensations only, (2) mixed sensations (both auditory and nonauditory), (3) side effect (nonauditory sensations), or (4) no sensation. In addition, the sensations elicited by monopolar higher-rate pulse-train stimuli similar to that used in processor programming were measured for all electrodes in the ABI array and classified using the same categories. Comparisons were made between evoked response morphology, bipolar stimulation sensation, and monopolar stimulation sensation. RESULTS: Sensations were classified for 33 bipolar pairs as follows: 21 pairs were auditory, 6 were mixed, 5 were side effect, and 1 was no sensation. When these sensations were compared with the electrically evoked response morphology for these signals, P3 of the electrically evoked auditory brainstem response (eABR) and the presence of a middle-latency positive wave, usually between 15 and 25 msec (electrical early middle-latency response [eMLR]), were only present when the perceptual sensation had an auditory component (either auditory or mixed pairs). The presence of other waves in the early-latency response such as N1 or P2 or a positive wave after 4 msec did not distinguish between only auditory or only nonauditory sensations. For monopolar stimulation, 42 were classified as auditory, 16 were mixed, and 26 were classified as side effect or no sensation. When bipolar sensations were compared with monopolar sensations for the 21 bipolar pairs categorized as auditory, 7 pairs had monopolar sensations of auditory for both electrodes, 9 pairs had only one electrode with a monopolar sensation of auditory, with the remainder having neither electrode as auditory. Of 6 bipolar pairs categorized as mixed, 3 had monopolar auditory sensations for one of the electrodes. When monopolar stimulation was compared with evoked potential morphology elicited by bipolar stimulation, P3 and the eMLR were more likely to be present when one or both of the electrodes in the bipolar pair elicited an auditory or mixed sensation with monopolar stimulation and were less likely to occur when neither of the electrodes had an auditory monopolar sensation. Again, other eABR waves did not distinguish between auditory and nonauditory sensations. CONCLUSIONS: ABI electrodes that are associated with auditory sensations elicited by bipolar stimulation are more likely to elicit evoked responses with a P3 wave or a middle-latency wave. P3 of the eABR and M15-25 of the eMLR are less likely to be present if neither electrode of the bipolar pair evoked an auditory sensation with monopolar stimulation.

Challenges for stem cells to functionally repair the damaged auditory nerve.

INTRODUCTION: In the auditory system, a specialized subset of sensory neurons are responsible for correctly relaying precise pitch and temporal cues to the brain. In individuals with severe-to-profound sensorineural hearing impairment these sensory auditory neurons can be directly stimulated by a cochlear implant, which restores sound input to the brainstem after the loss of hair cells. This neural prosthesis therefore depends on a residual population of functional neurons in order to function effectively. AREAS COVERED: In severe cases of sensorineural hearing loss where the numbers of auditory neurons are significantly depleted, the benefits derived from a cochlear implant may be minimal. One way in which to restore function to the auditory nerve is to replace these lost neurons using differentiated stem cells, thus re-establishing the neural circuit required for cochlear implant function. Such a therapy relies on producing an appropriate population of electrophysiologically functional neurons from stem cells, and on these cells integrating and reconnecting in an appropriate manner in the deaf cochlea. EXPERT OPINION: Here we review progress in the field to date, including some of the key functional features that stem cell-derived neurons would need to possess and how these might be enhanced using electrical stimulation from a cochlear implant.

[Direct recording from cochlear nerve via a ball-electrode in transtemporal acoustic neuroma surgery]. / Direkte Ableitung vom Nervus cochlearis bei transtemporaler Resektion von Vestibularisschwannomen.

BACKGROUND: Intraoperative monitoring (IOM) of the cochlear nerve function during acoustic neuroma surgery is employed to assist in preserving hearing. So far, Auditory Brain-stem Response (ABR) is considered to be an optimal method for intraoperative monitoring in transtemporal approach. The aim of this study was to perform direct recording of the cochlear nerve action potential after resection of the tumor by using a ball-electrode and to evaluate the use of this method in predicting the postoperative hearing. The obtained data were compared to the simultaneous ABR results and to the postoperative hearing. MATERIAL AND METHODS: In 2009, 38 patients have undergone acoustic Neuroma Surgery at the ENT University hospital, Wuerzburg. In 33 patients an intraoperative ABR as well as a direct measurement from the cochlear nerve using a ball electrode were performed. In 5 patients the postoperative hearing was predicted using the direct measurement at the cochlear nerve only. RESULTS: The direct recording from the cochlear nerve gave very robust responses. Even in cases where ABR recording was not possible, the identification of clear cochlear nerve action potential could still be reached. Using the direct recordings from the cochlear nerve to predict the post operative hearing turned out to have a sensitivity of 100% and a specificity of 70%. CONCLUSIONS: These results show that intraoperative monitoring with direct recording from the cochlear nerve via a ball-electrode in transtemporal approaches offers a valuable method to predict the postoperative hearing. Further investigation will be made to provide additional information.

Role of stromal cell-derived factor-1 expression in the injured mouse auditory nerve.

OBJECTIVE: The degeneration of hair cells and spiral ganglion neurons (SGNs) is an important pathologic process in the development of sensorineural hearing loss. In a murine model, predictable and reproducible damage to SGNs occurs through the application of ouabain to the round window. Recent evidence has shown that the chemokine stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant of hematopoietic stem cells (HSCs) and provides trophic support to injured tissues during development and maturation. The hypothesis for the current study is that expression of SDF-1 plays an important role in protecting SGNs and preventing further degeneration in the setting of cochlear injury. STUDY DESIGN: Prospective, controlled. SETTING: Academic research laboratory. SUBJECT AND METHODS: Auditory brainstem response (ABR) and the expression of SDF-1 mRNA and protein were examined 1, 3, 7, 14, and 30 days after application of ouabain in 35 adult mice. RESULTS: Following ouabain application, real-time reverse-transcription polymerase chain reaction for SDF demonstrates increased mRNA expression following ouabain injury in nontransplanted mice. A significant increase in SDF protein expression was also observed using immunolabeling techniques and Western blot analysis. CONCLUSIONS: SDF-1 expression is increased in the auditory nerve following cochlear injury. Further knowledge about the cochlear microenvironment, including SDF-1, is critical to maximizing HSC engraftment in the injured cochlea and providing a therapeutic option for sensorineural hearing loss.

Ventral petrous meningiomas: unique tumors.

INTRODUCTION: This study aims to analyze our experience with petrous meningiomas (PM), testing the hypothesis that these tumors have different histologic subtypes and operative outcome depending on the site of origin in reference to the internal auditory canal (IAC). METHODS: Fifty-eight patients with PM were reviewed retrospectively. Tumors were classified as posterior (PPM; n = 29), superior (SPM; n = 8), and ventral petrous (VPM; n = 19), in reference to the IAC. Two patients had multiple meningiomas arising from different parts of the petrous bone. Petroclival, clival, and jugular tubercle meningiomas were excluded. All patients were operated through a suboccipital retrosigmoid approach. Clinical presentation, tumor size, involvement of IAC, extent of resection, outcome, and tumor histology were analyzed. RESULTS: Simpson grade I and II resection was achieved in 84.5%: 96.6% in PPM, 100% in SPM, and 57.9% in VPM. Fibrous histology accounted for 69% in PPM, 62% in SPM, and only 10.5% in VPM, whereas meningothelial histology was seen 27.6%, 25%, and 68.4%, respectively. Postoperative hearing loss was the most frequent operative complication, and was seen in 31.6% of VPM, as compared to none in PPM or SPM. CONCLUSIONS: Ventral petrous meningiomas are clearly different tumors in their histology and operative outcome. The predominance of meningothelial histology in this location may imply a different tumorigenesis as compared to other PM. Ventral petrous meningiomas should be viewed as a distinct group of tumors.

[Identification of the cochlear nerve in surgical removal of vestibular schwannomas].

Review of methods which allow intraoperative identifying and monitoring of cochlear and facial nerves in resection of vestibular schwannomas is presented. We describe a case of successful identification and functional preservation of facial and cochlear nerves in a patient with acoustic neuroma. Detailed description of neurophysiological and neurosurgical aspects of surgical technique intended to preserve auditory functions is given. According to some authors, application of intraoperative neurophysiological techniques in surgery of vestibular schwannomas allows to preserve not only anatomical but also functional integrity of neural structures as well.

Intraoperative brainstem auditory evoked potential pattern and perioperative vasoactive treatment for hearing preservation in vestibular schwannoma surgery.

OBJECTIVE: In vestibular schwannoma surgery, four different intraoperative brainstem auditory evoked potential (BAEP) patterns (stable BAEP, abrupt loss, irreversible progressive loss, reversible loss) can be identified and correlated with postoperative hearing outcome. Patients with reversible loss significantly benefit from postoperative vasoactive treatment consisting of hydroxyethyl starch and nimodipine. The present study investigates the treatment effect in the remaining three BAEP patterns. METHODS: A retrospective analysis was performed in 92 patients operated on for vestibular schwannoma between 1997 and 2005. Between 1997 and 2001, only patients with reversible loss of BAEP received vasoactive medication. Subsequently, all patients operated on between 2001 and 2005 received a 10 day course of therapy, regardless of the BAEP pattern. Serial audiological examinations before, after surgery and after 1 year were performed in all patients. RESULTS: All 30 patients with reversible loss of BAEP received medication, and postoperative hearing preservation was documented in 21 patients. All 13 patients with stable waves showed hearing preservation, regardless of treatment. In all 24 patients with abrupt loss and in all 25 patients with irreversible progressive loss, postoperative anacusis was documented, regardless of treatment. CONCLUSION: In patients with reversible loss of BAEP, a disturbed microcirculation of the cochlear nerve seems to be the underlying pathophysiological factor. In patients with abrupt or irreversible progressive loss, additional mechanical injury of nerve fibres determines hearing outcome. The study provides evidence that for the purpose of hearing preservation, only patients with reversible loss of BAEP benefit from vasoactive treatment.

Lithium increases bcl-2 expression in chick cochlear nucleus and protects against deafferentation-induced cell death.

Approximately 20-30% of neurons in the avian cochlear nucleus (nucleus magnocellularis) die following deafferentation (i.e. deafness produced by cochlea removal) and the remaining neurons show a decrease in soma size. Cell death is generally accepted to be a highly regulated process involving various pro-survival and pro-death molecules. One treatment that has been shown to modify the expression of these molecules is chronic administration of lithium. The present experiments examined whether lithium treatment can protect neurons from deafferentation-induced cell death. Post-hatch chicks were treated with LiCl or saline for 17 consecutive days, beginning on the day of hatching. On the 17th day, a unilateral cochlea ablation was performed. Five days following surgery, the nucleus magnocellularis neurons were counted stereologically on opposite sides of the same brains. Lithium reduced deafferentation-induced cell death by more than 50% (9.8% cell death as compared with 22.4% in saline-treated subjects). Lithium did not affect cell number on the intact side of the brain. Lithium also did not prevent the deafferentation-induced decrease in soma size, suggesting a dissociation between the mechanisms involved in the afferent control of soma size and those involved in the afferent control of cell viability. A possible mechanism for lithium's neuroprotective influence was examined in a second set of subjects. Previous studies suggest that the pro-survival molecule, bcl-2, may play a role in regulating cell death following deafferentation. Tissues from lithium- and saline-treated subjects were examined using immunocytochemistry. Chronic administration of lithium dramatically increased the expression of bcl-2 protein in nucleus magnocellularis neurons. These data suggest that lithium may impart its neuroprotective effect by altering the expression of molecules that regulate cell death.

Preservation of the auditory nerve function after translabyrinthine removal of vestibular schwannoma.

OBJECTIVE: To evaluate the function of the postoperative auditory nerve preserved after translabyrinthine (TL) vestibular schwannoma (VS) removal. METHODS: Fifteen patients, who underwent unilateral VS resection via a TL approach, were preserved auditory nerve anatomically. The size and location of VS were measured on MRI preoperatively. After surgery, the electrical stimulation test (EST) or electrically evoked auditory brainstem response (EABR) was performed. RESULTS: Four cases (27%) out of fifteen patients were retained the functional integrity of the auditory nerve after surgery. The maximum tumor size in the group with a positive response to EST or EABR was significantly smaller than that in the group with a negative response to EST. It seems to be difficult to preserve auditory nerve function in cases where a tumor extends to the fundus of internal auditory canal. CONCLUSION: These results suggest that size of tumor and/or extension of tumor to the fundus might be important factors in preserving the auditory nerve function even if using a TL approach.

Brainstem auditory evoked potential monitoring: when is change in wave V significant?

BACKGROUND: The probability of hearing loss during cerebellopontine angle (CPA) surgery can be reduced by using brainstem auditory evoked potential (BAEP) intraoperative monitoring (IOM). A wave V latency prolongation of 1.0 milliseconds or amplitude decrement of greater than 50% is arbitrarily considered the point when damage to hearing occurs. OBJECTIVE: To determine the accuracy of wave V changes in predicting hearing impairment. METHODS: Patients undergoing BAEP IOM for surgery in the CPA region were evaluated. The greatest wave V latency and amplitude change was determined. Patients were divided into four groups depending on degree of change of wave V: Group 1 consisted of minimal change, whereas Group 4 was permanent loss of wave V. The frequency of hearing loss in each group was compared. RESULTS: Data from 156 patients were reviewed. When all patients were analyzed, the frequency of hearing loss was not significantly different between the groups. When patients with CPA tumor were excluded, a significantly higher number of patients in Group 4 had hearing loss. Analysis of the patients with CPA tumor showed no difference in the frequency of hearing loss in any of the groups; even a large number (50%) of Group 1 patients had hearing impairment. CONCLUSIONS: During brainstem auditory evoked potential intraoperative monitoring, the type of surgery is important when interpreting significance of changes of wave V. For non-cerebellopontine angle tumor surgery, hearing loss occurs usually only with permanent loss of wave V; much smaller changes may be important in cerebellopontine angle tumor surgery.

Microvascular decompression for primary hemifacial spasm. Importance of intraoperative neurophysiological monitoring.

There is considerable evidence that primary Hemi-Facial Spasm (HFS) is in almost all cases related to a vascular compression of the facial nerve at its Root Exit Zone (REZ) from brainstem, and that Micro-Vascular Decompression (MVD) constitutes its curative treatment. Clinical as well as electrophysiological features plead for mechanisms of the disease in structural lesions at the neural fibers (putatively: focal demyelination at origin of ephapses) and functional changes in the nuclear cells (hyperactivity of the facial nucleus). Lateral Spread Responses (LSRs) elicited by stimulation of the facial nerve branches testify of these electrophysiological perturbations. Monitoring LSRs during surgery is feasible; however the practical value of their intraoperative disappearance as control-test of an effective decompression remains controversial.MVD allows cure of the disease in most cases. Because the VIIIth nerve is at risk during surgery, intraoperative monitoring of Brainstem Auditory Evoked Potentials (BEAPs) is of value to reduce occurrence of hearing loss. Increase in latency of Peak V and decrease in amplitude of Peak I are warning-signals of an excessive stretching of the the cochlear nerve and impairment of the cochlear vascular supply, respectively.

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. The electrophysiological and morphological results of our study indicated that M-CSF could ameliorate both anterograde (Wallerian) and retrograde degeneration in both the CNS and PNS portions of the auditory nerve. We attribute the success of M-CSF therapy to the reported functional dichotomy (having the potential to cause both neuroprotective and neurotoxic effects) of microglia and macrophages. Whether the activities of microglia/macrophages are neuroprotective or neurotoxic may depend upon the nature of the stimulus that activates the cells. In the present study, the neuroprotective effects of M-CSF that were observed could have been due to M-CSF we administered and to M-CSF released from endothelial cells, resident cells of the CNS parenchyma, or infiltrating macrophages. Another possibility is that M-CSF ameliorated apoptotic auditory neuronal death, although this hypothesis remains to be proved in future studies.

Experimental vibratory damage of the inner ear.

The aim of the experiment was to determine the effect of whole-body vibration on the inner ear. The investigations were carried out on 40 guinea pigs, subjected to sinusoidal vibration (10 Hz/5 mm/1.4 g rms) for 1 to 6 months in a noiseless apparatus. Cochlear microphonic measurements were done with a phase-sensitive detection technique for the levels 70, 80 and 90 dB and the frequencies of 0.26, 0.5, 1 and 2 kHz from the apex of the cochlea and for 4 and 8 kHz from the region of the round window. Analysis of 1,440 measurements suggested the possibility of damage appearing in the upper turnings of the cochlea. The subsequent morphological analysis was based on the estimation of the state of the hair cells (a three-degree scale of injury) in a Zeiss DSM 950 scanning microscope and of the structure of the fibers of the acoustic nerve in a Zeiss EM 900 transmission microscope. Vibration-induced changes were seen in all the examined inner ears of the experimental groups. Hair-cell damage was more often seen in the region of the apex, spreading gradually in the direction of the base and from the circumference (outer hair cells of the third row) to the modiolus. The most characteristic vibrational changes of the acoustic nerve fibers occurred in 100% of the examined myelin sheaths and were visible as decreases in their electrodensity. The changes in both the assessed elements of the inner ear appeared simultaneously but independently and were directly connected with the duration of the experiment. The results obtained allow an explanation of the mechanism of hearing loss in persons subjected to whole-body vibration. The damages done to the inner ear structures may cause a worsening of hearing there, especially in the low and medium frequencies.

Auditory brainstem implant in posttraumatic cochlear nerve avulsion.

Patients aged over 12 years with neurofibromatosis type 2 are considered candidates for an auditory brainstem implant (ABI). This study extends the indication criteria of ABI to subjects with profound hearing loss due to damaged cochleas and/or cochlear nerves (CNs) following head injuries. In our department, over the period from April 1997 to November 2002, 32 patients, 23 adults and 9 children, were fitted with ABIs. Their ages ranged from 14 months to 70 years. These patients were suffering from a variety of tumor (13 subjects) and nontumor CN or cochlear diseases (19 subjects). Six patients, 5 adults and 1 child, had profound hearing loss following head injury. Their mean age was 25 years (range: 16-48 years). Five were male and 1 female. The retrosigmoid approach was used in all 6 patients. The electrode array was inserted into the lateral recess of the fourth ventricle and correct electrode positioning was monitored with the aid of electrically evoked auditory brainstem responses and neural response telemetry. Correct implantation was achieved in all patients. No complications were observed due to implantation surgery or related to ABI activation and stimulation of the cochlear nuclei. At activation, an average of 9.8 electrodes (range 5-13) were switched on without side effects. One to 6 electrodes were activated in the following sessions after time periods ranging from 2 to 16 months. All patients achieved auditory-alone-mode closed-set word recognition scores ranging from 40 to 100%; 3 had auditory-alone-mode open-set sentence recognition scores of 60-100%; 2 of these even had speech-tracking performance scores of 38 and 43 words, respectively, showing an ability to engage in normal conversation and converse over the phone. The present study demonstrates that the ABI is a useful rehabilitation instrument in subjects with damaged cochleas and/or CN avulsion following head injury who are unamenable or poorly responsive to auditory rehabilitation using cochlear implants.