Faculty Bibliography

In comparison to the extensive study of skin wound healing, there have been few reports investigating mucosal wound healing. Our primary objective was to compare the natural progression of wound healing in airway mucosa to skin in a rabbit model. Split-thickness skin wounds and subglottic mucosal wounds created by drill injury were compared on days 0, 1, 3, 5, 7, 14 and 21 after injury. Histologic examination was performed by a veterinary pathologist blinded to sample identity. Subglottic wounds showed a 'fibrinous clot' overlying the epithelium, analogous to the fibrin crust in skin wounds. Re-epithelialization started on day 5 in the subglottic epithelium and was complete by day 14; fibroplasia and fibrosis in the lamina propria were present on days 7-21. This wound healing profile paralleled the skin epidermis and dermis, respectively. The epithelial changes, however, were temporally extended in the airway. Our secondary objective was to determine the effects of treating airway mucosa with a bioresorbable membrane, modified sodium hyaluronate and carboxymethylcellulose (modified HA/CMC), placed over the subglottic wounds of four rabbits after drill injury. Subglottic wounds treated with modified HA/CMC showed a more mature epithelium and less fibrosis on day 21. In this pilot study, the application of a bioresorbable membrane improved mucosal wound healing at both the epithelial and lamina propria levels. Clearly, a larger study must be performed to confirm this interesting observation

We reviewed our experience with 100 children admitted to Children's Hospital of Pittsburgh between 1980 and 1995 with an intratemporal complication of acute otitis media. Seventy-two patients were treated for acute mastoiditis. Of these 72 children, 54 (75.0%) were treated conservatively with broad-spectrum intravenous antibiotics and myringotomy. Eighteen (25.0%) required mastoidectomy for treatment of a subperiosteal or Bezold's abscess or cholesteatoma, or because of poor response to conservative therapy. Twenty-two children presented with facial paralysis, complete in 5 (22.7%) and incomplete in 17 (77.3%). Eighteen (81.8%) were treated conservatively, but four required mastoid surgery. Nineteen patients had adequate follow-up; of these, 15 recovered normal facial function but 4 were left with partial paralysis. Three patients presented with serous labyrinthitis and recovered completely with conservative therapy. Of the two patients who presented with suppurative labyrinthitis, one was treated conservatively, but the other required tympanomastoidectomy with cochleotomy; both patients had permanent, profound sensorineural hearing loss in the affected ear. Four patients presented with acute petrositis, and in all four it resolved with mastoidectomy. In the antibiotic era, intratemporal complications of acute otitis media still occur in otherwise healthy children, often after inadequate treatment of acute otitis media

The central nucleus of the inferior colliculus (ICC) receives direct inputs, bilaterally, from all auditory brain stem nuclear groups. To evaluate the contribution made to gerbil ICC neuron physiology by two major afferent pathways, we examined the synaptic responses evoked by direct stimulation of the commissure of the inferior colliculus (CIC) and the ipsilateral lateral lemniscus (LL). Frontal midbrain slices were obtained from postnatal day (P) 9-P19 gerbils, and whole cell recordings were made under current- (n = 22) or voltage-clamp (n = 52) conditions. Excitatory and inhibitory synaptic responses were characterized by sequentially exposing the slice to ionotropic glutamate receptor antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + aminophosphonpentanoic acid (AP-5), or kynurenic acid)], a gamma-aminobutryic acid type A receptor antagonist (bicuculline), and a glycine receptor antagonist (strychnine). In current clamp, LL stimulation typically produced a short latency depolarization followed by a longer duration hyperpolarization. The depolarization was abolished by AP-5 + CNQX, and the remaining inhibitory potential displayed either bicuculline or strychnine sensitivity. In voltage clamp, 79% of ICC neurons displayed synaptic currents after stimulation of each pathway. The synaptic currents were typically complex waveforms, and ionotropic glutamate receptor antagonists reduced inward currents at a holding potential of -80 mV in the majority of neurons. In addition, this treatment reduced outward synaptic currents at a holding potential of -20 mV, indicating that inhibitory interneuronal input was often activated by LL or CIC afferents. A minority of neurons had synaptic currents that were unaffected by glutamate receptor antagonists, but it was more common for CIC-evoked currents to be unaffected (38%) rather than LL-evoked currents (22%). The CIC provided a strong inhibitory input that was almost exclusively GABAergic, whereas the LL inhibition often included a glycinergic component. These experiments have shown that the CIC provides a major glutamatergic and GABAergic input to most ICC neurons. However, much of the inhibitory input from both the CIC and the LL appears to be mediated by interneuronal connections

The principal role of ionotropic glutamate receptors in the transmission and processing of information in the auditory pathway has been investigated extensively. In contrast, little is known about the functional contribution of the G-protein-coupled metabotropic glutamate receptors (mGluRs), although their anatomic location suggests that they exercise a significant influence on auditory processing. To investigate this issue, sound-evoked responses were obtained from single auditory neurons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionophoretic pipettes. In general, microionophoresis of the mGluR agonists, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionotropic agonists, such as N-methyl--aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminished after administration of the mGluR antagonist, (+)-alpha-methyl-4-carboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed after the mGluR agonist had been discontinued for several minutes. Approximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular property observed in other systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the sound-evoked response similar to the cellular phenomenon of long-term potentiation. These findings suggest that mGluR activation has a profound influence on the gain of primary afferent driven activity in the caudal cochlear nucleus

GABAergic and glycinergic circuits are found throughout the auditory brainstem, and it is generally assumed that transmitter phenotype is established early in development. The present study documents a profound transition from GABAergic to glycinergic transmission in the gerbil lateral superior olive (LSO) during the first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical stimulation of the medial nucleus of the trapezoid body (MNTB), a known glycinergic projection in adult animals. GABAergic and glycinergic components were identified by blocking transmission with bicuculline and strychnine (SN), respectively. In the medial limb of LSO, there was a dramatic change in the GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12% at P12-P16. There was an equal and opposite increase in the glycinergic component during this same period. Direct application of GABA also elicited significantly larger amplitude and longer duration responses in P3-P5 neurons compared with glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons were more sensitive to SN throughout development. Consistent with the electrophysiological observations, there was a reduction in staining for the beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine receptor-associated protein gephyrin increased. Brief exposure to baclofen depressed transmission at excitatory and inhibitory synapses for approximately 15 min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data demonstrate a striking switch from GABAergic to glycinergic transmission during postnatal development. Although GABA and glycine elicit similar postsynaptic ionotropic responses, our results raise the possibility that GABAergic transmission in neonates may play a developmental role distinct from that of glycine

Synaptic activity plays an important role in many aspects ofneuronal development, particularly the expression of proteins. In this study, the influence of inhibitory and excitatory afferents on the development of glycine receptor density in the lateral superior olive (LSO) of Mongolian gerbils was investigated. Afferent activity was manipulated by removing one or both cochleas at postnatal day 7, prior to the onset of sound-evoked responses. Due to the anatomy of the LSO, these manipulations result in either excitatory denervation, inhibitory denervation, or both. The density of glycine receptors in the LSO was determined at 21 days postnatal. Glycine receptors were either labeled with tritiated strychnine (3H-SN) or with an antibody directed against gephyrin, a protein closely associated with the receptor complex. Antibody binding was used to quantify the differential glycine receptor density between the medial limb (high frequency area) and the lateral limb (low frequency area) of the LSO. 3H-SN was used to quantify the amount of glycine receptors in each part of the LSO in control and experimental animals. In addition, changes in neuron density and neuron cross-sectional area were quantified following cochlear ablations. In control animals, the amount of glycine receptors is about 2- to 3-fold higher in the high-frequency than in the low-frequency region. In bilaterally ablated animals, the same density of glycine receptors was measured in the high- and low-frequency region. Unilateral ablations had no significant effect on glycine receptor distribution, either ipsi- or contralateral to the ablation. The neuron cross-sectional area decreased about 30% in the ipsilateral LSO of unilaterally ablated animals and in bilaterally ablated animals. However, alterations of soma density and cross-sectional area were similar in the high- and low-frequency projection region. These results suggest that the distribution of glycine receptors is only changed when excitatory and inhibitory afferents have been denervated

Inhibitory synaptic transmission is of fundamental importance during the maturation of central auditory circuits, and their subsequent ability to process acoustic information. The present study investigated the manner in which inhibitory transmission regulates intracellular free calcium levels in the gerbil inferior colliculus using a brain slice preparation. Inhibitory and excitatory postsynaptic potentials were evoked by electrical stimulation of the ascending afferents at the level of the dorsal nucleus of the lateral lemniscus. Pharmacologically isolated inhibitory synaptic potentials were able to attenuate a calcium rise in collicular neurons that was generated by depolarizing current injection. In addition, GABA(A) and glycine receptor antagonists typically led to an increase of calcium in collicular neurons during electrical stimulation of the ascending afferent pathway at the level of the dorsal nucleus of the lateral lemniscus. Bath application of GABA or muscimol, a GABA(A) receptor agonist, evoked a brief hyperpolarization followed by a long-lasting depolarization in inferior colliculus neurons. This treatment also induced a transient calcium increase that correlated with the membrane depolarization phase. Baclofen, a GABA(B) receptor agonist, had no effect on either membrane potential or calcium levels. Ratiometric measures indicated that the muscimol-evoked rise in calcium was approximately 150 nM above basal levels. The muscimol-evoked responses were completely antagonized by bicuculline and attenuated by picrotoxin. Together, these results suggest that inhibitory synaptic transmission participates in the regulation of postsynaptic calcium during the developmental period. Inhibitory transmission may attenuate a calcium influx that is evoked by excitatory synapses, but it can also produce a modest influx of calcium when activated alone. These mechanisms may help to explain the influence of inhibitory transmission on the development of postsynaptic properties

We have recently discovered a paradoxical aftereffect associated with inhibition in the gerbil auditory midbrain. Single neurons in the inferior colliculus (IC) were assessed for sensitivity to a virtual motion stimulus produced by modulating the interaural level difference (ILD), a major cue for sound localization. The class of neuron studied was predominantly excited by contralateral stimulation and inhibited by ipsilateral stimulation. Sound pressure level was modulated trapezoidally at the ipsilateral 'inhibitory' ear, whereas the contralateral 'excitatory' level remained constant. When the inhibitory stimulus was decreased within a range of sound levels that maintained suppression under static conditions, an unexpected discharge was often elicited, apparently because of an aftereffect of synaptic inhibition. In contrast, when the inhibitory stimulus was increased within a range of sound levels that produced only modest suppression under static conditions, neuronal discharge was often profoundly suppressed. In many cases the 'conditioned enhancement' or 'conditioned suppression' persisted for several seconds after the modulation of ILD, and such conditioned responses were influenced by the modulation depth and rate. To test the effect of inhibition in the IC directly, glycine and GABA were pulsed from a glass recording pipette during a constant monaural excitatory stimulus. The acoustically elicited discharge rate was potentiated markedly if preceded immediately by the brief (0.5-10 sec) application of inhibitory transmitter. Collectively, these results revealed unusually long-lasting effects of inhibition that may establish a new range of acoustic cues to which the neuron responds best. This may have broad implications for processing ensuing auditory stimuli

Thin Silastic sheet alloplasts (Dow Corning, Midland, MI, U.S.A) are commonly used to reconstruct posttraumatic orbital floor defects. Complications associated with orbital Silastic implantation include infection, migration, and extrusion. The authors report an unusual case of an intraorbital, squamous, epithelial-lined cyst appearing as progressive vertical globe dystopia and proptosis occurring after Silastic reconstruction of a traumatic orbital floor defect

OBJECTIVE: The purpose of this cadaver dissection was to study the position of the auriculotemporal nerve in relation to the mandibular condyle, capsular tissues, articular fossa, and lateral pterygoid muscle and to evaluate the anatomic possibility of nerve impingement or irritation by the surrounding structures. STUDY DESIGN: Eight cadaveric heads (16 sides) were dissected. The auriculotemporal nerve was identified by following its course around the middle meningeal artery. The course of the nerve trunk was dissected from the middle meningeal artery to the terminal branches within the temporomandibular disk. The horizontal distance between the auriculotemporal nerve and the medial portion of the condyle/condylar neck was measured. The vertical distance from the most superior portion of the articular condyle to the superior border of the auriculotemporal nerve was measured. RESULTS: The auriculotemporal nerve was identified on each side, and a single trunk was evident along the medial aspect of the condylar neck. At the posterior border of the lateral pterygoid muscle, the nerve trunk was in direct contact with the condylar neck in every specimen. The average vertical distance between the superior condyle and the nerve was 7.06 mm (+/- 3.21 mm); the range was 0 to 13 mm. The vertical distance between the nerve and the superior condyle on one side of the specimen did not correlate with the distance on the contralateral side. CONCLUSION: The auriculotemporal nerve trunk has a close anatomic relationship with the condyle and the temporomandibular joint capsular region, and there is evidence of a possible mechanism for sensory disturbances in the temporomandibular joint region. In all cases, the nerve was in direct contact with the medial aspect of the capsule or condylar neck. Because there is no correlation between the positions of the nerves on the right and left sides, only one side may be affected. The nerve was also observed to course in direct apposition to the lateral pterygoid muscle. The findings support the hypothesis that the anatomic and clinical relationship of the auriculotemporal nerve to the condyle, articular fossa, and lateral pterygoid muscle may be causally related to compression or irritation of the nerve, producing numbness or pain, or both, in the temporomandibular joint region