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Skull base trauma: diagnosis and management.

The singular anatomical relationship of the base of the skull is responsible for the particular problems that may arise after injury. Extensive dural laceration and severe neurovascular damage may accompany skull base injuries. Trauma to the anterior skull base is frequently related to the paranasal sinuses, and trauma to the middle and the posterior skull base usually affects the petrous bone. Injury to the anterior fossa including the paranasal sinuses may produce CSF leakage, damage the olfactory nerves, optic nerves, and orbita contents. Fractures may affect the carotid canal, injure the internal carotid artery and result in carotid-cavernous fistula. Trauma to the petrous bone may cause facial palsy and deafness, and CSF leakage with otorrhoea or paradoxal rhinoliquorrhoea. Trauma to the posterior fossa may lacerate the major venous sinuses, and affect the cranio-cervical stability. Each one of these injuries will need a particular strategy. Decision making for management as a whole must consider all aspects, including the fact that these injuries frequently involve polytraumatized patients. Decisions regarding the timing of surgery and the sequence of the surgical procedures must be made with great care. Modern surgical techniques and recent technologies including functional preservation of the olfactory nerves in frontobasal trauma, visual evoked potentials, assisted optic nerve decompression, facial nerve reconstruction, interventional technique for intravascular repair of vascular injuries, and recent developments in cochlea implants and brain stem implants, all contributed significantly to improve outcome and enhance the quality of life of patients. This article reviews basic principles of management of skull base trauma stressing the role of these advanced techniques.

Cerebrospinal Fluid Otorrhea↗

Olfactory ensheathing glia and Schwann cells: two of a kind?

Both olfactory ensheathing cells (OECs) and Schwann cells have been shown to promote axonal regrowth and remyelination in the central (CNS) and peripheral nervous systems under experimental conditions. During development, OECs and Schwann cells emerge from the olfactory placode and the neural crest, respectively, thus sharing a common "peripheral" origin. Both cell types are known to express a number of different molecular markers in common, to display a similar morphological phenotype in culture and to respond to the same growth-promoting molecules. Contrary to Schwann cells, OECs are found in association with neuronal processes in the CNS constituting the olfactory nerve layer of the olfactory bulb. OECs maintain their growth-promoting capacity in the CNS during adult life supporting the lifelong axonal growth of olfactory receptor neurons. Thus, OECs are considered an intermediate cell type combining a "central" location with "peripheral" permissiveness. Recently, the regenerative potential of OECs has been demonstrated in a variety of studies. However, OECs are still less clearly defined than Schwann cells. On designing future therapeutical strategies for nerve injury and disease, the important question arises as to whether OECs and Schwann cells are comparable cell types or whether they, indeed, mediate specific effects, making either the one or the other suitable for special applications. The present review summarizes recent data on the in vitro and in vivo properties of OECs and critically compares the analogies and differences in the biology of both cell types relevant in the above-mentioned context.

Animals↗

Large mechanical changes in the bullfrog olfactory bulb evoked by afferent fiber stimulation.

The isolated olfactory bulb of the bullfrog responds to olfactory nerve stimulation with large mechanical changes in the bulb. The sequence of these changes represents: (1) swelling of the bulb associated with action potential production in the secondary neurons; (2) shrinkage during powerful inhibition of the secondary neurons; and (3) swelling accompanied by repetitive firing of action potentials in the bulb. The effects of bicuculline and Cl-free Ringer on these mechanical changes were examined. The shrinkage of the bulb is closely related with the inhibitory postsynaptic potentials (IPSPs) in the mitral cells.

Action Potentials↗

The nervous supply to the nasal cavity of the Bactrian camel (Camelus bactrianus).

The Bactrian camel is an important domestic animal in some of the desert and semi-desert areas of the world. However, there is no detailed report about the nervous supply to the nasal cavity of the Bactrian camel. In the present study, seven heads of adult Bactrian camels were collected and the nerve distribution in the nasal cavity was dissected grossly. The results demonstrated that the nerves supplying to the nasal cavity included the olfactory nerve, the ethmoidal nerve from the ophthalmic nerve, and the caudal nerve from the maxillary nerve. The general patterns of nervous distribution in the nasal cavity of the Bactrian camel corresponded with those of other domestic animals. However, the terminal nerve was not observed by this gross anatomical method in the Bactrian camel.

Animals↗

Electron microscopy of colocalization of GABA and tyrosine hydroxylase expression in rat olfactory bulb transplants.

Juxtaglomerular (JG) neurons of rat olfactory bulb (OB) are a subset of inhibitory interneurons within the OB, acting via lateral inhibition to modulate the afferent input of the primary olfactory nerve. The JG neurons, composed of periglomerular, external tufted, and short axon cells, have been found to express various neurotransmitters, including gamma-amino butyric acid (GABA) and dopamine. A specific set of neurons within the periglomerular population have also been shown to coexpress these neurotransmitters. Deafferentation or functional odor deprivation of the normal OB causes a loss of tyrosine hydroxylase (TH) (the rate limiting enzyme in the dopamine synthesis pathway) expression within the JG cell population, but appears to have no effect on GABA levels. Our laboratory has developed a transplantation model to further study the effects of deafferentation and subsequent reinnervation within this system. Sections from transplant (TX) OBs were reacted for GABA and TH using immunocytochemical localization protocols and studied by electron microscopy. Numerous neuronal populations were found to be either TH or GABA positive in this study, with a specific subpopulation showing colocalization of both. Although the architecture of the TX OB is somewhat disrupted and the TH- and GABA-positive cells were not as uniform in their arrangement as they are in the normal OB, we found that these cells in the TX OB were morphologically similar to the JG cells of normal OB. Positively labeled profiles were also found to receive and form numerous synaptic contacts with both host olfactory nerve axons as well as with the processes of donor neurons. These synaptic contacts were within areas that resemble the glomeruli of normal OB, suggesting that lateral inhibition may occur within the TX OB as it does in the normal. The coexpression of GABA and TH within specific neurons also indicates that a unique population of JG neurons that occur in normal OB are also found within this transplanted system as well.

Animals↗

Cerebrospinal fluid absorption in the rabbit: olfactory pathways.

Twenty rabbits were intrathecally perfused with horseradish peroxidase (HRP) without increasing the cerebrospinal fluid (CSF) pressure. Histologic and ultrastructural studies of the olfactory nerve and nasal mucosa showed HRP along the space between peri- and epineurium down to the smaller nerve branches in the mucosa. Within the mucosa, HRP leaked out from the epineurium and flowed into: (a) lymphatic vessels; (b) mucous glands and ducts; (c) intercellular spaces of the nasal pseudostratified nasal epithelium; and (d) venules. These findings could account for "bulk" flow CSF absorption into the lymphatic system, the nasal cavity, and to a lesser degree, the venous system; also explain CSF rhinorrhea in man and experimental animals; as well as lymphatic drainage of CSF into cervical lymph nodes.

Absorption↗

[Somatotopic relations between the olfactory mucosa and the olfactory bulb in the triton].

The axons of receptors located in the olfactory neuroepithelium are known to synapse with mitral cell dendrites in the glomerular layer of the ipsilateral olfactory bulb, but few previous studies showed a clear-cut topological organization of this projection. We therefore injected horseradish peroxidase (HRP) into restricted areas of the olfactory mucosa in adult tritons, Triturus cristatus. The animals were perfused with glutaraldehyde 17 h later; the mucosa, the olfactory nerve and bulb were removed, serially cut and treated with diaminobenzidine to reveal the localization and extent of the injection and the areas in the glomerular layer of the bulb to which the injected HRP had been transported by anterograde axonal flow. Small injections of HRP tended to label a small area in the bulb, while larger injections projected to a wider zone. The results also indicated the existence of an orderly projection, with a transposition of the dorso-ventral axis of the neuroreceptor sheet into an essentially anteroposteriorly oriented axis in the bulb. Thus, the dorsally located areas of the olfactory mucosa project to the most anterior part of the glomerular layer, whereas the vomero-nasal mucosa, which is located near the most lateral part of the ventral mucosa, projections to the posterior enlargement of the glomerular layer in the bulb. The data also showed that nerve bundles within the olfactory nerve maintain are orderly position which depends upon their origin. It is postulated that this somatopic organization reflects the development undergone by the peripheral olfactory system during ontogenesis.

Animals↗

Phosphate efflux and oxygen consumption in small non-myelinated nerve fibres at rest and during activity.

1. The oxygen consumption and the movements of labelled phosphate were measured in garfish olfactory nerve at rest and during activity.2. In solutions with 2.5 mM-K and 0.2 mM-phosphate the resting oxygen consumption was 0.206 m-mole/kg.min; activity at 2 sec(-1) produced an extra oxygen consumption of 2.46 mumole/kg.impulse. The extra oxygen consumption declined exponentially with a time constant of 2.62 min at 22-26 degrees C.3. The phosphate efflux, measured simultaneously, had a resting efflux rate constant of 1.24 x 10(-3) min(-1); activity at 2 sec(-1) produced an extra fractional loss of 9.38 x 10(-6) impulse(-1). The increase in phosphate efflux followed almost the same time course as the increase in oxygen consumption.4. Increasing the frequency of stimulation from 2 sec(-1) to 3 or 5 sec(-1) decreased both the extra oxygen consumption and the extra fractional loss of phosphate. When the frequency was decreased to 0.5 or 1 sec(-1) the extra oxygen consumption per impulse increased, while the extra phosphate liberation was lowered.5. Changing the phosphate concentration did not much affect the extra oxygen consumption; on the other hand, lowering or increasing the phosphate from the standard 0.2 mM decreased both the resting and the stimulated phosphate efflux.6. Lowering the K from the standard 2.5 mM did not affect the extra oxygen consumption, but increased both the resting and the extra loss of phosphate. At higher K concentrations the extra oxygen consumption and the extra fractional loss of phosphate decreased without much change in the resting phosphate efflux.7. Application of 1-20 muM-strophanthidin produced a transient decrease in the resting phosphate efflux without much change in resting oxygen consumption. With 10 or 20 muM-strophanthidin the extra fractional loss of phosphate and the extra oxygen consumption were both lowered in approximately the same proportions.8. The findings are consistent with the hypothesis that the increase in intracellular inorganic phosphate that results from increased break-down of ATP after activity, is the main cause for the increased phosphate efflux. A fraction of the increase in intracellular phosphate only appears to be liberated to the outside, the value of the fraction depending on the resting phosphate efflux before activity.9. The initial increase in intracellular inorganic phosphate after an impulse, estimated from the oxygen consumption or the phosphate fluxes, appears to be about 12-19 mumole/kg nerve, remarkably close to the value known from chemical analysis.

Animals↗

Peripheral anosmia attenuates female-enhanced aggression in male rats.

It is well established that male rats with prior access to sexually active females show enhanced offensive aggression toward unfamiliar male intruders. The present study assessed the importance of the sense of smell for this facilitatory effect. It was found in 2 independent experiments that anosmia, induced peripherally by surgically removing the olfactory epithelium and cutting the olfactory nerves, reduced baseline levels of offensive aggression and significantly attenuated the female-enhanced aggression effect. It was also found that sexual performance of anosmic rats was context-dependent, in that it was more impaired in the homecage environment than in standard observation cages. In contrast to sham-operated males, the experimental animals showed no preference for estrous over anestrous females in a mate choice test. Anosmic males did not appear more fearful than controls, as assessed in a hyponeophagia test, but they showed less exploratory behavior (rearing and head-dipping) in the hole-board test, and less rearing activity in automated activity boxes.

Aggression↗

An intracellular analysis of dendrodendritic inhibition in the turtle in vitro olfactory bulb.

1. Intracellular recordings from an in vitro preparation of turtle olfactory bulb were used to determine the pathway responsible for producing synaptic inhibition of mitral cells.2. Inhibitory post-synaptic potentials (i.p.s.p.s) could be elicited in mitral cells by both olfactory nerve (orthodromic) and mitral cell axon (antidromic) stimulation and by suprathreshold depolarizing current pulses injected intracellularly through the recording micro-electrode. Reversing the chloride gradient by either intracellular injection of chloride or lowering the external chloride concentration reversed the i.p.s.p.s into depolarizing potentials. The GABA antagonists, bicuculline and picrotoxin, blocked the i.p.s.p.s.3. A large increment in the size of the orthodromic and antidromic i.p.s.p. was associated with an action potential. Grading the stimulus intensity on either side of threshold resulted in graded changes in the size of the i.p.s.p. The increment associated with an action potential and the ability to evoke an i.p.s.p. by direct stimulation of a mitral cell suggested that these phenomena were due to activation of the dendrodendritic reciprocal synapses between mitral and granule cells.4. Orthodromic, antidromic and directly produced action potentials could be fractionated such that regenerative activation of the soma-dendritic membrane could be blocked. Only when this membrane was allowed to reach threshold was a large i.p.s.p. recorded. This indicated that the increment in the i.p.s.p. was due to activation of a synaptic pathway involving the soma-dendritic membrane.5. When spike propagation in the mitral cell axons was blocked by tetrodotoxin (TTX), an i.p.s.p. could still be produced by direct stimulation, indicating that the mitral cell soma-dendritic membrane is functionally both pre- and post-synaptic. TTX blocked the fast, high amplitude somatic spikes and revealed higher threshold, broader spikes of lower amplitude that were blocked by cobalt and calcium-free Ringer.6. Tetraethylammonium (TEA) increased the duration and the amplitude of the calcium spike. The amplitude was also increased by barium which prolonged the spike only if TEA was present. In the presence of TEA, bicuculline also prolonged the calcium spike. This suggests that three ionic conductances limit the duration of the calcium action potential: a voltage-dependent potassium conductance, a calcium-dependent potassium conductance, and the chloride conductance associated with the i.p.s.p.7. Spontaneous, bicuculline-sensitive, depolarizing potentials were recorded in mitral cells impaled with KCl-filled electrodes. Orthodromic or antidromic stimulation increased the frequency of these small potentials for the duration of the i.p.s.p., indicating prolonged GABA release.8. Stimulation of the olfactory nerves, the mitral cell axons, and direct stimulation could elicit action potentials in granule layer cells. Orthodromic and antidromic activation was followed by a hyperpolarization of about the same duration as the mitral cell i.p.s.p. and was probably the result of dysfacilitation.9. Paired stimulation of the mitral cell axons resulted in the diminution of the granule cell e.p.s.p. evoked by the second shock, indicating that the predominant excitatory input to the granule cells is through the mitral cell dendrites.10. It is concluded that both synaptic inhibition of mitral cells and excitation of granule cells is mediated primarily by the dendrodendritic reciprocal pathway.

Action Potentials↗

Non-conventional role of lysosomal acid phosphatase in olfactory receptor axons: co-localization with growth-associated phosphoprotein-43.

Olfactory receptor neurons undergo a continuous turnover in adult mammals. It is largely unknown how their axons invade the olfactory bulb and induce synaptic re-organization in glomeruli. Here, the cytochemical localization of lysosomal acid phosphatase has been studied in olfactory bulbs of adult rats and mice. The enzyme has been identified by specific substrate, inhibitors and absence in lysosomal acid phosphatase-knockout mice. Lysosomal acid phosphatase is located in primary and secondary lysosomes, which are unevenly distributed in the olfactory nerve layer and among olfactory glomeruli. In consecutive sections of glomeruli, the intensity of lysosomal acid phosphatase immunoreactivity co-varied with that of growth-associated phosphoprotein. Electron microscopically, differential lysosomal acid phosphatase staining in glomeruli corresponded to different proportions of labelled and unlabelled axons. Quantification revealed that lysosomal acid phosphatase labelling was strongest in non-synaptic profiles of terminal axons, while it was weak in or even missing from most synaptic profiles. Hence, growing olfactory axons apparently carry more lysosomal acid phosphatase than those which have established synaptic contacts. Following olfactory deafferentation both lysosomal acid phosphatase activity and growth-associated phosphoprotein-43 are lost from glomeruli, suggesting that both proteins are expressed in olfactory sensory axons during growth, while lysosomal acid phosphatase is apparently not a marker of anterograde terminal degeneration.

Acid Phosphatase↗

The binding of labelled saxitoxin to the sodium channels in nerve membranes.

1. Tritium labelled saxitoxin has been prepared and purified, and its binding both to intact rabbit vagus nerves and to a solubilized preparation of garfish olfactory nerve membranes has been examined.2. In intact and solubilized nerves there is a saturable binding component of magnitude equal to that previously obtained for labelled tetrodotoxin.3. This component of bound saxitoxin is displaced competitively by tetrodotoxin, and it is concluded that the two toxins bind to the same site.4. The saturable saxitoxin (STX) interaction with the nerve membrane is reversible and can be described by the equation STX + R right harpoon over left harpoon STX.R where R is the binding site or receptor. With the solubilized preparation of garfish nerve membranes the saxitoxin-receptor reaction rates are almost four times faster than those of tetrodotoxin. The half-life of the saxitoxin-receptor complexes is 13 sec compared with 44 sec for the tetrodotoxin-receptor complex.5. A number of agents were tested for their ability to displace the labelled saxitoxin. Calcium and thallous ions each produced significant reversible reduction in binding, with apparent equilibrium dissociation constants of about 20-30 mM. Toxin binding is also inhibited reversibly in acidic solutions by protons competing with toxin for a binding site with a pK(a) of 5.6-5.9. All three ions are known to block sodium currents in myelinated nerve at similar concentrations. Our experiments indicate that they do so at the site of toxin binding.6. Lidocaine and veratrine do not affect the binding of saxitoxin.

Animals↗

Hyposmia following laryngectomy: experimental model.

Hyposmia following laryngectomy is a well-known clinical observation, yet the causes have been controversial for many years. In an attempt to resolve this issue, an animal model was constructed. Eighteen dogs were divided into three equal groups: control dogs, dogs that underwent tracheostomy, and dogs that underwent tracheostomy and denervation of the larynx, simulating total laryngectomy. Four to 6 months following these operations, biopsies from olfactory mucosa were taken. The results showed marked changes in the olfactory mucosa of the two test groups: cystic degeneration of secretory glands in the olfactory mucosa of the first group and involution of the olfactory mucosa, substituted by dense connective tissue and "ballooning" of olfactory nerve fibres in the second group. These findings suggest that the changes in olfactory mucosa are not only caused by a loss of nasal airway but also the existence of a neurologic connecting network between the vagus nerve and the olfactory cortex.

Animals↗

Olfactory receptor neurons express D2 dopamine receptors.

The role of the dopamine (DA) in the olfactory bulb (OB) was explored by determining which of the potential target cells express dopamine receptors (DARs). Previously, it was reported that D2-like DAR (D2, D3, and D4 subtypes) radioligand binding is restricted to the outer layers of the OB. The neuronal elements present only in these layers are the axons of the olfactory receptor neurons (ORNs) and the juxtaglomerular (JG) neurons of the glomerular layer. Based on this pattern of D2-like ligand binding, it was suggested that D2-like receptors might be located presynaptically on ORN terminals. The present study was undertaken to investigate this hypothesis. In the outer bulb layers of rats in which the ORNs were destroyed by nasal lavage with ZnSO(4), D2-like radioligand binding was reduced severely. The receptor subtype D2 mRNA, but not D3 mRNA, was detected in adult rat olfactory epithelial tissue. By using in situ hybridization, this D2 mRNA was located preferentially in epithelial layers that contain ORN perikarya. D2 mRNA was eliminated after bulbectomy, a manipulation known to cause retrograde degeneration of the mature ORNs. Taken together, the surgical manipulations indicate that mature ORNs express D2 DARs and are consistent with the hypothesis that functional receptors are translocated to their axons and terminals in the bulb. This suggests that dopamine released from JG interneurons could be capable of presynaptically influencing neurotransmission from the olfactory nerve terminals to OB target cells through the D2 receptor.

Animals↗

Comparative morphology and cytology of the olfactory organs in Moray eels with remarks on their foraging behavior.

BACKGROUND: This study compares the morphology and cytology of olfactory organs in moray eels (Muraenidae), particularly Siderea grisea and some species of the genera Echidna, Gymnothorax, and Lycodontis, fishes that are top predators in shallow-water marine habitats. Some of the species search visually for food while others search by olfaction. METHODS: The morays were collected in the Red Sea; the nasal olfactory organs were dissected and fixed in Bouin's solution for light-microscopy, and 3.5% glutaraldehyde for electron-microscopy studies. RESULTS: In each studied species the olfactory rosettes are elongated structures situated in closed olfactory chambers between anterior tubular inlet nares and slit-form posterior outlet openings. The double row of lamellae constituting these rosettes are round in Siderea and Echidna and elongated in the other species. They are attached at their base to a median raphe and range in number from 20 in the youngest observed Siderea to 168 in Gymnothorax of 1,500 mm total length. As in other teleosts, the lamellae are covered by a ciliated epithelium composed of three types of sensory cells: two of these, ciliated sensory neurons and ciliated supporting cells, differ in detail, length, and thickness of their cilia and intracellular rootlet system; the third type of sensory cells bears microvillae as well as cilia. Proximal, axonal extensions of the ciliated cells cross the basal lamina in bundles and combine to form fila olfactoria from which the two olfactory nerves extend towards the olfactory bulbs. Lateral extensions at the basal parts of these ciliated cells, the so-called spines, cross the membranes of neighboring cells as dendrites, possibly changing part of all of the ciliated epithelium into an olfactory field. The density and number of sensory cells on the lamellae, as well as observed differences in their foraging behavior in nature and captivity, enable the morays to be divided into two groups: one group, in which the lamellae are richly covered with stereocilia, includes species of the genera Siderea and Echidna, that search for food by olfaction, and the second group, which has a great deal less cells with stereocilia and includes the studies species of Gymnothorax and Lycodontis, locates its food visually.

Animals↗

Sexual dimorphism of the flounder Bothus robinsi (Pisces: Bothidae).

The anatomical organization of the reproductive system of the flounder, Bothus robinsi, is similar to other fish in the order Pleuronectiformes. Accentuated, external secondary sexual characters are observed in males such as increased body length, larger left pectoral fin, and greater interorbital distance. As a qualitative character, the rostral spine, which is part of the maxillary bone, is pronounced. The interorbital distance implies noticeable internal sexual differences, such as the broadening of the left frontal and lateral ethmoid bones, and a greater length of the oblique muscles of both eyes, the optic nerves, and the left olfactory nerve. Five male specimens examined had female external secondary sexual characters.

Animals↗

Ontogeny and distribution of gonadotropin-releasing hormone (GnRH) neuronal systems in the brain of the cichlid fish Cichlasoma dimerus.

Using immunocytochemistry we have described the distribution and ontogeny of three distinct gonadotropin-releasing hormone (GnRH) neural systems, emphasizing the analysis during the period of sex differentiation in the South American cichlid fish Cichlasoma dimerus. In the forebrain a group of neurones immunoreactive to salmon GnRH that formed clusters in the nucleus olfacto retinalis (NOR), was located at the junction of the olfactory bulb and the telencephalon. These neurones differentiated 3 days after fertilization from the olfactory placodes. GnRH immunoreactive neurones along the olfactory nerves through the rostrobasal olfactory bulb were observed on day 4 and at the NOR on day 10. A group of neurones immunoreactive to chicken GnRH II was seen in the dorsal midbrain tegmentum. They originate from the ventricular ependyma between days 5 and 6. These neurones remained close to blood vessels throughout development. Between days 22 and 30 a group of neurones immunoreactive to seabream GnRH was detected in the anterior basal preoptic area. GnRH innervation of the pituitary was detected after the differentiation of preoptic neurones and in coincidence with gonadal differentiation. We hypothesize that the GnRH neural systems have three distinct embryonic origins. Furthermore, we show that the NOR and the midbrain GnRH neurones might have functions other than gonadal development, whereas the preoptic GnRH neurones in C. dimerus might be associated with gonadal sex differentiation.

Animals↗

Amphibian olfactory receptor neurons express olfactory marker protein.

Expression of olfactory marker protein (OMP) in olfactory receptor neurons (ORNs) in two amphibians was investigated by immunohistochemical methods. The OMP immunoreactivity was observed in the cilia, apical dendritic knobs, dendrites and somas of ORNs; the axons of ORNs also showed intense immunoreactivity for OMP throughout their course from the olfactory epithelium to the glomerular layer of the olfactory bulb. Seven days after olfactory nerve transection in salamander, the number of OMP-positive ORNs was markedly reduced in the ipsilateral epithelium. The results demonstrate that amphibian ORNs express OMP and confirm its phylogenetic conservation across diverse species.

Ambystoma↗