Initial stages of development of the submandibular gland (human embryos at 5.5-8 weeks of development).

The aim of this study was to determine the main stages of submandibular salivary gland development during the embryonic period in humans. In addition, we studied submandibular salivary gland development in rats on embryonic days 14-16 and expression in the submandibular salivary gland region with the monoclonal antibody HNK-1. Serial sections from 25 human embryos with a greatest length ranging from 10 to 31 mm (Carnegie stages 16-23; weeks 5.5-8 of development) and Wistar rats of embryonic days (E) 14-16 were analysed with light microscopy. Five stages of submandibular salivary gland development were identified. The prospective stage (1), between weeks 5.5 and early week 6, is characterized by a thickening of the epithelium of the medial paralingual groove in the floor of the mouth corresponding to the primordium of the submandibular salivary gland parenchyma. At this stage, the primordium of the parasympathetic ganglion lies below the lingual nerve. The primordium of the submandibular salivary gland parenchyma is observed in rats on E14 in the medial paralingual groove with mesenchymal cells, underlying the lingual nerve. These cells are HNK-1-positive, corresponding to the primordium of the parasympathetic ganglion. The bud stage (2), at the end of week 6 in humans and on E15 in rats, is characterized by the proliferation and invagination of the epithelial condensation, surrounded by an important condensation of the mesenchyme. The pseudoglandular stage (3) at week 6.5 is characterized by the beginning of the formation of lobes in the condensed mesenchyme. The canalicular stage (4), between week 7 and 7.5, is characterized by the appearance of a lumen in the proximal part of the submandibular duct. The innervation stage (5) occurs during week 8, with the innervation of the submandibular and interlobular ducts. Nervous branches arriving from the parasympathetic ganglion innervate the glandular parenchyma. Numerous blood vessels are observed nearby. Our results suggest that submandibular salivary gland development requires interactions among epithelium, mesenchyme, parasympathetic ganglion and blood vessels.

Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic migraine.

Objective The main objective of this pilot study was to investigate the safety of administering onabotulinumtoxinA towards the sphenopalatine ganglion in 10 patients with intractable chronic migraine with an open, uncontrolled design. We also collected efficacy data to provide an indication as to whether future placebo-controlled studies should be performed. Method In a prospective, open-label, uncontrolled study after one-month baseline, we performed bilateral injections of 25 IU onabotulinumtoxinA (total dose 50 IU) toward the sphenopalatine ganglion in a single outpatient session in 10 patients with intractable migraine with a follow-up of 12 weeks. The primary outcome was adverse events and the main efficacy outcome was frequency of moderate and severe headache days in month 2 post-treatment compared to baseline. Results All 10 patients experienced a total of 25 adverse events. The majority of these were different types of local discomfort in the face and jaw, and none were classified as serious. In an intention-to-treat analysis of the main efficacy outcome, a statistically significant reduction of moderate and severe headache days in baseline versus month 2 was observed (16.3 ± 6.2 days baseline versus 7.6 ± 7.6 days month 2, p = 0.009). Eight out of 10 patients experienced an at least 50% reduction of moderate and severe headache days compared to baseline. Conclusion The result warrants randomised, placebo-controlled studies to establish both safety and efficacy of this potential novel treatment of chronic migraine.

Reduced salivary gland size and increased presence of epithelial progenitor cells in DLK1-deficient mice.

DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis. Here, we have extended our studies of the salivary gland phenotype of Dlk1 knock-out mice. We have observed that salivary glands are smaller and weigh significantly less in both Dlk1 knock-out males and females compared with gender and age-matched wild-type mice and regardless of the natural sexual dimorphism in rodent salivary glands. This reduced size correlates with a reduced capacity of Dlk1-deficient mice to secrete saliva after stimulation with pilocarpine. However, histological and ultrastructural analyses of both adult and developing salivary gland tissues have revealed no defects in Dlk1 ((-/-)) mice, indicating that genetic compensation accounts for the relatively mild salivary phenotype in these animals. Finally, despite their lack of severe anomalies, we have found that salivary glands from Dlk1-deficient mice present a higher amount of CK14-positive epithelial progenitors at various developmental stages, suggesting a role for DLK1 in the regulation of salivary epithelial stem cell balance.

Transoral submandibular ganglion neurectomy: an anatomical feasibility study.

BACKGROUND: The management of sialorrhea can be difficult for both the patient and the clinician. Current management includes behavioral modification, anticholinergics, botulinum injections, and a variety of surgical options, which all have demonstrated some efficacy. As minimally invasive procedures flourish, we explore the feasibility of highly selective transoral submandibular neurectomy (TOSN) for the management of sialorrhea. METHODS: Ten human cadaver dissections of the floor of mouth were performed bilaterally, for a total of 20 separate cases. An intraoral technique for highly selective, submandibular ganglion neurectomy is demonstrated. RESULTS: A transoral submandibular ganglion neurectomy was performed in 10 cadavers (20 neurectomies) easily and reliably, without injury to the submandibular duct or the main trunk of the lingual nerve. CONCLUSION: Transoral submandibular neurectomy is an attractive addition to the armamentarium of surgical options for the treatment of medically intractable sialorrhea. Further study in selected patients would need to be performed to demonstrate clinical feasibility.

Clinical course of patients with episodic cluster headache treated with corticosteroids inproximity to the sphenopalatine ganglion: a preliminary study of 23 patients.

OBJECTIVE: A study is made of the clinical course of patients with episodic cluster headache following the injection of corticosteroids in the proximity of the sphenopalatine ganglion of the affected side. STUDY DESIGN: A retrospective observation study was made corresponding to the period between 2006 and 2010. Patients with episodic cluster headache received corticosteroid infiltrations in the vicinity of the sphenopalatine ganglion. Data were collected to assess the clinical course, quantifying pain intensity and quality of life. A total of 23 patients (11 women and 12 men) with a mean age of 50.4 years (range 25-65) were included. Forty percent of the patients had undergone dental extractions in the quadrant affected by the pain, before the development of episodic cluster headache, and 37.8% underwent extractions in the same quadrant after appearance of the headache. RESULTS: Most of the patients suffered 1-3 attacks a day, with a duration of pain of between 31-90 minutes. The mean pain intensity score during the attacks at the time of the first visit was 8.8 (range 6-10), versus 5.4 (range 3-9) one week after the first corticosteroid injection. On the first visit, 86.9% of the patients reported unbearable pain, versus 21.7% after one week, and a single patient after one month. CONCLUSIONS: The evolution of episodic cluster headache is unpredictable and variable, though corticosteroid administration clearly reduces the attacks and their duration.

The pterygopalatine ganglion and its role in various pain syndromes: from anatomy to clinical practice.

The postsynaptic fibers of the pterygopalatine or sphenopalatine ganglion (PPG or SPG) supply the lacrimal and nasal glands. The PPG appears to play an important role in various pain syndromes including headaches, trigeminal and sphenopalatine neuralgia, atypical facial pain, muscle pain, vasomotor rhinitis, eye disorders, and herpes infection. Clinical trials have shown that these pain disorders can be managed effectively with sphenopalatine ganglion blockade (SPGB). In addition, regional anesthesia of the distribution area of the SPG sensory fibers for nasal and dental surgery can be provided by SPGB via a transnasal, transoral, or lateral infratemporal approach. To arouse the interest of the modern-day clinicians in the use of the SPGB, the advantages, disadvantages, and modifications of the available methods for blockade are discussed.▪

5-HT(1D) receptor immunoreactivity in the sphenopalatine ganglion: implications for the efficacy of triptans in the treatment of autonomic signs associated with cluster headache.

OBJECTIVE: To determine if 5-HT(1D) receptors are located in the sphenopalatine ganglion. BACKGROUND: While the 5-HT(1D) receptor has been described in sensory and sympathetic ganglia in the head, it was not known whether they were also located in parasympathetic ganglia. METHODS: We used retrograde labeling combined with immunohistochemistry to examine 5-HT(1D) receptor immunoreactivity in rat sphenopalatine ganglion neurons that project to the lacrimal gland, nasal mucosa, cerebral vasculature, and trigeminal ganglion. RESULTS: We found 5-HT(1D) receptor immunoreactivity in nerve terminals around postganglionic cell bodies within the sphenopalatine ganglion. All 5-HT(1D) -immunoreactive terminals were also immunoreactive for calcitonin gene-related peptide but not vesicular acetylcholine transporter, suggesting that they were sensory and not preganglionic parasympathetic fibers. Our retrograde labeling studies showed that approximately 30% of sphenopalatine ganglion neurons innervating the lacrimal gland, 23% innervating the nasal mucosa, and 39% innervating the trigeminal ganglion were in apparent contact with 5-HT(1D) receptor containing nerve terminals. CONCLUSION: These data suggest that 5-HT(1D) receptors within primary afferent neurons that innervate the sphenopalatine ganglion are in a position to modulate the excitability of postganglionic parasympathetic neurons that innervate the lacrimal gland and nasal mucosa, as well as the trigeminal ganglion. This has implications for triptan (5-HT(1D) receptor agonist) actions on parasympathetic symptoms in cluster headache.

Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice.

Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.

Endoscopic study for the pterygopalatine fossa anatomy: via the middle nasal meatus-sphenopalatine foramen approach.

OBJECTIVE: The purposes of this study were to locate the constant anatomic landmarks, which are very important and helpful for endoscopic surgery and not well described for the pterygopalatine fossa (PPF) surgery via the middle nasal meatus-sphenopalatine foramen approach to establish a safe surgical mode. METHODS: Eight cases of adult skull specimens were selected for the simulated surgery. The Messerklinger surgical approach was used under the endoscope. The uncinate process was removed successively, and the anterior ethmoid sinus and posterior ethmoid sinus were opened. The opening of the maxillary sinus was identified and was expanded forward and backward. The ethmoidal crest was found and was used as an anatomic landmark to find the sphenopalatine foramen. The sphenopalatine artery was protected and was used as a guide to enter the PPF region. The sphenopalatine artery was followed conversely to anatomize the blood vessels and nerves in the PPF. RESULTS: It was found that our surgical procedure provides a clear view of the constant anatomic landmark including ethmoidal crest and sphenopalatine foramen. By retrograde dissection, following the sphenopalatine artery, which runs out of the sphenopalatine foramen behind the ethmoidal crest, the internal maxillary artery (IMA) and the branches of the IMA in the PPF were exposed. Posterior to the sphenopalatine artery, the typical Y-shaped structure with the pterygopalatine ganglion as the center was visible when the IMA and its branches were moved downward and outward. The Y structure, which is consisted of the pterygopalatine ganglion, branches of the internal maxillary nerve, vidian nerve, and descending palatine nerve, served as the other anatomic landmark. By following the Y structure, it was easy to locate the pterygoid canal, foramen rotundum, and the infraorbital nerve, and the integrity of the nerve structure could be protected. CONCLUSION: Endoscopic PPF surgery via the middle nasal meatus-sphenopalatine foramen approach is safe, and the ethmoidal crest, sphenopalatine foramen, and Y structure with the pterygopalatine ganglion in the center are important anatomic landmarks that can be referred to during the surgery.

Neuromuscular dentistry and the role of the autonomic nervous system: Sphenopalatine ganglion blocks and neuromodulation. An International College of Cranio Mandibular Orthopedics (ICCMO) position paper.

The Sphenopalatine Ganglion (SPG) is known to play an integral role in the pathophysiology of a wide variety of orofacial pains involving the jaws, sinuses, eyes and the trigeminal autonomic cephalalgias. It supplies direct parasympathetic innervation to the trigeminal and facial nerves. Sympathetic innervation from the superior sympathetic chain passes thru the SPG to the trigeminal and facial nerves.This paper reviews relevant and significant literature on SPG Blocks and Neuromodulation published in peer reviewed medical and dental journals. Neuromuscular Dentistry employs ULF-TENS to relax musculature and simultaneously provide neuromodulation to the ganglion.Conclusion: The effects of ULF-TENS on the autonomic nervous system acts on the Limbic System and Hypothalamus (H-P-A) to address Axis II issues during neuromuscular dental procedures. It also directly affects the autonomic component of the trigeminal nerve involved in almost all headaches and migraines as well as the Myofascial and Joint disorders of TMD.

Developmental abnormalities of the otic capsule and inner ear following application of prolyl-hydroxylase inhibitors in chick embryos.

BACKGROUND: Naturally hypoxic conditions in amniote embryos play important roles in normal development. We previously showed that a hypoxic condition is required to produce a sufficient amount of neural crest cells (NCCs) during embryogenesis and that promoting a hypoxic response by prolyl-hydroxylase (PHD) inhibitors increases NCCs. Given that PHD inhibitors are considered as a potential treatment for anemia and ischemic diseases, we investigated the phenotypic effect of PHD inhibitors on embryonic development. METHODS: Chick embryos were administered with PHD inhibitors prior to the induction of NCCs on day 1.5. Three main events relating to hypoxia, NCCs induction, vasculogenesis and chondrogenesis, were examined. RESULTS: PHD inhibitors caused an increase of Sox10-positive NCCs in vivo. Vasculogenesis was promoted temporarily, although rapid vasculogenesis diminished the effect by day 5 in cephalic and pharyngeal regions. Studies on chondrogenesis at day 7 showed advanced development of the otic capsule, a cartilaginous structure encapsulating the inner ear. Analysis by X-ray micro-computed-tomography (µCT) revealed smaller otic capsule, suggesting premature differentiation. This in turn, deformed the developing semicircular canals within it. Other skeletal structures such as the palate and jaw were unaffected. The localized effect on the otic capsule was considered a result of the multiple effects from the hypoxic responses, increased NCCs and promoted chondrogenesis. CONCLUSION: Given the wide range of clinical applications being considered for PHD inhibitors, this study provides crucial information to caution and guide use of PHD inhibitors when treating women of childbearing age.

A computed tomography scan and anatomical cadaveric study of the pterygopalatine ganglion for use in Gamma Knife treatment of cluster headache.

OBJECT: Gamma Knife surgery has recently been used to treat patients with cluster headaches. Both the trigeminal nerve root and the pterygopalatine ganglion (PPG) have been targeted. However, there are no clear-cut anatomical landmarks on computed tomography (CT) scans or magnetic resonance images that accurately identify the PPG. Therefore, the authors performed microsurgical dissections on latex-injected cadaver heads to expose the PPG and correlated the findings with thin-slice axial CT scans obtained in the same heads to determine how best to target the PPG. METHODS: Three cadaver heads (five sides) previously injected with colored latex were dissected using skull base approaches and microsurgical techniques to identify the PPG and surrounding structures. Measurements were then made to different osseous anatomical landmarks such as the foramen rotundum, vidian canal, and so on. The PPG was marked with a radiopaque marker and thin-slice CT scans were obtained in the cadaver heads to develop some correlates that could be used to identify where the PPG is located on CT scans. RESULTS: The PPG was clearly identified in all specimens and had a mean diameter of 3.58 +/- 0.6 mm. The PPG was always located in the same plane (lateral and vertical) as the vidian canal and was located on average 2.7 +/- 0.3 mm from the end of the canal. The vidian canal was clearly identified on coronal CT scans and had a diameter of 3.05 mm. CONCLUSIONS: There was a clear and constant relationship between the PPG and vidian canal. The vidian canal is easily identified on coronal CT scans and can be used as a landmark to target the PPG with the Gamma Knife.

[Atypical facial pains--sluder's neuralgia--local treatment of the sphenopalatine ganglion with phenol--case report]. / Nietypowe bóle twarzy--neuralgia sludera-- leczenie miejscowe--przyieganie zwoju skrzydlowo-- podniebiennego fenolem--opis przypadków.

AIM: Chronic reccuring head and facial pain can be very difficult for successful treatment. Such a pain can be in some rare cases Sluder's sphenopalatine ganglion neuralgia. The aim of the study was to obtain the pain relief by local treatment in patients with Sluder's sphenopalatine ganglion neuralgia. METHODS: We described three cases of Sluder's neuralgia among all the seventeen patients with reccuring head and face pain that were seen in our department. In all these cases 4% Xylocaine was applied intranasally, into the region of shenopalatine ganglion, behind the posterior tip of the middle turbinate four times for ten minutes. According to Kern, the diagnosis of Sluder's neuralgia was confirmed only in cases where local anesthetic block of the sphenopaltine ganglion was successful. It means the patients were pain-free for at least an hour after application of Xylocaine, so they were qualified for phenolization and 88% phenol was applied on the cotton carriers (number of the applications depended on the patient). RESULTS: The total relief of pain of different duration was obtained in all the presented cases. CONCLUSION: The relief of pain obtained by intranasal phenolization of sphenopalatine ganglion in three patients shows it could be the effective treatment of Sluder's neuralgia. The patients were totally free from the pain and accompanying symptoms like nasal obstruction, rhinorrhea, epiphora or conjunctivitis. The relief period was different but the patients were satisfied with the effectiveness and simplicity of the treatment. They did not need to take the additional medications for months and were able to continue work.

The pterygopalatine ganglion, palatine nerves and vessels: dissection and pathway / El ganglio pterigopalatino, nervios palatinos y vasos: disección y trayecto

SUMMARY: Background and Objectives: The palatine nerves and vessels cross the pterygopalatine fossa, the palatine canals, the palatine foramina and the submucosal space, at the level of the hard palate and the palatine recess of the maxillary sinus. Their trajectory is long, complicated and difficult to highlight on a single dissection piece. In the literature that we studied, we did not find clear images that fully highlight the real configuration of the pterygopalatine ganglion and nerves and of the palatine vessels. Our aim was to provide a clear and representative dissection of the pterygopalatine ganglion and of the palatine neurovascular bundle throughout its pathway in a simple, coherent and useful presentation for the practitioners interested in the regional pathology. We resected the posterior and inferomedial osseous walls of the maxillary sinus and highlighted the neurovascular structures in the pterygopalatine fossa and the wall of the maxillary sinus. We photographed the dissection fields and detailed the important relations. The images that we obtained are clear, simple and easy to interpret and use. We successfully highlighted the aspect and the main relations of the pterygopalatine ganglion and the pathway and distribution of the palatine nerves and vessels, from their origin to the terminal plexuses. There is a broad spectrum of clinical procedures or situations that require a proper knowledge and understanding of the anatomical pathway and relations of the palatine neurovascular elements. This includes the various types of regional anesthesia, tumor resection surgery, flaps of the palatine mucosa, the LeFort osteotomy etc. Demonstration of the pterygopalatine ganglion and its relations is useful in endoscopic interventions at the level of the pterygopalatine fossa.

RESUMEN: Los nervios y vasos palatinos atraviesan la fosa pterigopalatina, además de los canales palatinos, los forámenes palatinos y el espacio submucoso a nivel del paladar duro y el receso palatino del seno maxilar. Su trayectoria es larga, complicada y difícil de destacar en una sola pieza de disección. En la literatura que estudiamos, no encontramos imágenes claras que resalten completamente la configuración real del ganglio y los nervios pterigopalatinos y de los vasos palatinos. Nuestro objetivo fue proporcionar una disección clara y representativa del ganglio pterigopalatino y del haz neurovascular palatino a lo largo de su trayecto en una presentación simple, coherente y útil para los médicos interesados en la patología regional. Resecamos las paredes óseas posterior e inferomedial del seno maxilar y resaltamos las estructuras neurovasculares en la fosa pterigopalatina y la pared del seno maxilar. Fotografiamos los campos de disección y detallamos las relaciones importantes. Las imágenes que obtuvimos son claras, sencillas y de fácil interpretación. Resaltamos con éxito el aspecto y las principales relaciones del ganglio pterigopalatino y el trayecto y distribución de los nervios y vasos palatinos, desde su origen hasta los plexos terminales. En conclusion, existe un amplio espectro de procedimientos o situaciones clínicas que requieren un adecuado conocimiento y comprensión del trayecto anatómico y las relaciones de los elementos neurovasculares palatinos. Esto incluye los distintos tipos de anestesia regional, cirugía de resección tumoral, colgajos de mucosa palatina, osteotomía de LeFort, etc. La demostración del ganglio pterigopalatino y sus relaciones es útil en intervenciones endoscópicas a nivel de la fosa pterigopalatina.

Sphenopalatine ganglion pulsed radiofrequency treatment in patients suffering from chronic face and head pain.

PURPOSE: There are various facial pain syndromes including trigeminal neuralgia, trigeminal neuropathic pain and atypical facial pain syndromes. Effectiveness of the pulsed radiofrequency in managing various pain syndromes has been clearly demonstrated. There are a limited number of studies on the pulsed radiofrequency treatment for sphenopalatine ganglion in patients suffering from face and head pain. The purpose of this study is to evaluate the satisfaction of pulsed radiofrequency treatment at our patients retrospectively. METHODS: Infrazygomatic approach was used for the pulsed radiofrequency of the sphenopalatine ganglion under fluoroscopic guidance. After the tip of the needle reached the target point, 0.25-0.5 ms pulse width was applied for sensory stimulation at frequencies from 50 Hz to 1 V. Paraesthesias were exposed at the roof of the nose at 0.5-0.7 V. To rule out trigeminal contact that led to rhythmic mandibular contraction, motor stimulation at a frequency of 2 Hz was applied. Then, four cycles of pulsed radiofrequency lesioning were performed for 120 s at a temperature of 42°C. RESULTS: Pain relief could not be achieved in 23% of the patients (unacceptable), whereas pain was completely relieved in 35% of the patients (excellent) and mild to moderate pain relief could be achieved in 42% of the patients (good) through sphenopalatine ganglion-pulsed radiofrequency treatment. CONCLUSION: Pulsed radiofrequency of the sphenopalatine ganglion is effective in treating the patients suffering from intractable chronic facial and head pain as shown by our findings. There is a need for prospective, randomized, controlled trials in order to confirm the efficacy and safety of this new treatment modality in chronic head and face pain.

Technical and surgical aspects of the sphenopalatine ganglion (SPG) microstimulator insertion procedure.

Cluster headache (CH) is a debilitating, severe form of headache. A novel non-systemic therapy has been developed that produces therapeutic electrical stimulation to the sphenopalatine ganglion (SPG). A transoral surgical technique for inserting the Pulsante SPG Microstimulator into the pterygopalatine fossa (PPF) is presented herein. Technical aspects include detailed descriptions of the preoperative planning using computed tomography or cone beam computed tomography scans for presurgical digital microstimulator insertion into the patient-specific anatomy and intraoperative verification of microstimulator placement. Surgical aspects include techniques to insert the microstimulator into the proper midface location atraumatically. During the Pathway CH-1 and Pathway R-1 studies, 99 CH patients received an SPG microstimulator. Ninety-six had a microstimulator placed within the PPF during their initial procedure. Perioperative surgical sequelae included sensory disturbances, pain, and swelling. Follow-up procedures included placement of a second microstimulator on the opposite side (n=2), adjustment of the microstimulator lead location (n=13), re-placement after initial unsuccessful placement (n=1), and removal (n=5). This SPG microstimulator insertion procedure has sequelae comparable to other oral cavity procedures including tooth extractions, sinus surgery, and dental implant placement. Twenty-five of 29 subjects (86%) completing a self-assessment questionnaire indicated that the surgical effects were tolerable and 90% would make the same decision again.

Membrane lipid rafts are necessary for the maintenance of the (alpha)7 nicotinic acetylcholine receptor in somatic spines of ciliary neurons.

Calcium-permeable neurotransmitter receptors are concentrated into structurally and biochemically isolated cellular compartments to localize calcium-mediated events during neurotransmission. The cytoplasmic membrane contains lipid microdomains called lipid rafts, which can gather into microscopically visible clusters, and thus the association of a particular protein with lipid rafts can result in its redistribution on the cell surface. The present study asks whether lipid rafts participate in the formation and maintenance of the calcium-permeable alpha7-subunit nicotinic acetylcholine receptor (alpha7nAChR) clusters found in somatic spines of ciliary neurons. Lipid rafts and alpha7nAChR become progressively colocalized within somatic spines during synaptogenesis. To determine whether these rafts are required for the maintenance of alpha7nAChR aggregates, cholesterol was extracted from dissociated ciliary neurons by treatment with methyl-beta-cyclodextrin. This treatment caused the dispersion of lipid rafts and the redistribution of alpha7nAChR into small clusters over the cell surface, suggesting that the integrity of lipid rafts is required to maintain the receptor clustering. However, lipid raft dispersion also caused the depolymerization of the F-actin cytoskeleton, which can also tether the receptor at specific sites. To assess whether interaction between rafts and alpha7nAChR is independent of F-actin filaments, the lipid raft patches were stabilized with a combination of the cholera toxin B subunit (CTX), which specifically binds to the raft component ganglioside GM1, and an antibody against CTX. The stabilized rafts were then treated with latrunculin-A to depolymerize F-actin. Under these conditions, large patches of CTX persisted and were colocalized with alpha7nAChR, indicating that the aggregates of receptors can be maintained independently of the underlying F-actin cytoskeleton. Moreover, it was found that the alpha7nAChR is resistant to detergent extraction at 4 degrees C and floats with the caveolin-containing lipid-rich fraction during density gradient centrifugation, properties that are consistent with a direct association between the receptor and the membrane microdomains.

Value of intra- and post-operative cone beam computed tomography (CBCT) for positioning control of a sphenopalatine ganglion neurostimulator in patients with chronic cluster headache.

INTRODUCTION: The objective of this study was to determine whether postoperative control of the neurostimulator placement within the pterygopalatine fossa (PPF) by means of 3-dimensional (3D) cone beam computed tomography (CBCT) was of therapeutic relevance compared to intraoperative CBCT imaging alone. MATERIAL AND METHODS: Immediately after implantation of the sphenopalatine ganglion (SPG) neurostimulator, intraoperative CBCT datasets were generated in order to visualize the position of the probe within the PPF. Postoperatively, all patients received a CBCT for comparison with intraoperatively acquired radiographs. RESULTS: Twenty-four patients with cluster headache (CH) received an SPG neurostimulator. In 4 patients, postoperative CBCT images detected misplacement not found in intraoperative CBCT. In 3 cases, electrode tips were misplaced into the maxillary sinus and in 1 case into the apex of the PPF superior to the suspected location of the SPG. Immediate revision with successful repositioning within 3 days was done in 2 patients and a deferred reimplantation in 1 patient within 6 months. One patient declined revision. CONCLUSION: We were able to demonstrate the clinical value of postoperative dental CBCT imaging with a wide region of interest (ROI) due to a superior image quality compared with that achieved with intraoperative medical CBCT. Although intraoperative 3D CBCT imaging of electrode placement is helpful in the acute surgical setting, resolution is, at present, too low to safely exclude misplacement, especially in the maxillary sinus. High-resolution postoperative dental CBCT allows rapid detection and revision of electrode misplacement, thereby avoiding readmission and recurrent tissue trauma.

Localization of preganglionic neurons that innervate choroidal neurons of pterygopalatine ganglion.

PURPOSE: The pterygopalatine ganglion (PPG) receives preganglionic input from the superior salivatory nucleus (SSN) of the facial motor complex and is the main source of parasympathetic input to the choroid in mammals. The present study was undertaken to determine in rats the location and neurotransmitters of SSN neurons innervating those PPG neurons that target the choroid and to determine the location and neurotransmitters of the PPG choroidal neurons themselves. METHODS: Retrograde labeling from rat choroid using a fluorescent tracer, in combination with immunofluorescence labeling for nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP), and choline acetyltransferase (ChAT), was used to characterize the location and neurotransmitters of choroidal PPG neurons. To identify SSN neurons that innervate the choroidal PPG neurons, the Bartha strain of the retrograde transneuronal tracer pseudorabies virus (PRV-Ba) was injected into rat choroid, and immunolabeling for NOS or ChAT was used to characterize their neurochemistry. RESULTS: Fluorescent retrograde labeling showed that PPG neurons projecting to the choroid contained NOS, VIP, and ChAT and were widely distributed in PPG and its preganglionic root, the greater petrosal nerve. SSN neurons were ChAT(+), and a subset of them was found to contain NOS. PRV-Ba transneuronal retrograde labeling revealed that choroidal preganglionic neurons were localized to the rostral medioventral part of the ipsilateral SSN. The choroidal SSN neurons were ChAT(+) and appeared largely to correspond to the NOS(+) neurons of the SSN. CONCLUSIONS: These results show that preganglionic neurons in rats that are presumed to regulate choroidal blood flow through the PPG reside within the rostral medioventral SSN, and that NOS is a marker for these SSN neurons.

The efferent system of cranial nerve nuclei: a comparative neuromorphological study.

A number of inconsistencies and controversies are inherent in the classification of cranial nerve nuclei based on the concepts of the various head-theories. The assumption of head segmentation, which is common to these theories, serves as the basis for designating the dorsomedial nuclei as the somatomotor column, although they innervate striated muscles of a viscus and a specific sense organ. The ventrolateral nuclei are called the specific visceromotor column; they innervate striated muscles in the branchiogenous area, but many of these muscles insert on skeletal elements. A series of comparative neuromorphological studies investigating the dendritic arborization pattern and axonal trajectory in the frog, lizard, and rat suggests a much more delicate classification in which nine morphologically and functionally different neuron groups can be discerned: 1. The hypoglossal nucleus appears coincidentally with the muscular tongue in amphibia. The spindle-shaped perikaryon, the bipolar dendritic arborization, and the straight ventral trajectory of the axon are characteristic morphological features in all three animal species investigated. 2. The oculomotor, trochlear, and abducens nuclei present a remarkably conservative topography and organization in all vertebrates with a moving eye. With their oval-shaped or polygonal perikarya and radiating dendritic arborization, these neurons distinctly differ from hypoglossal neurons. The ipsilateral axons follow a straight ventral course, the contralateral axons form a dorsal loop before crossing the midline, and the crossing is not consequence of neuron migration to the contralateral side. 3. The accessory abducens nucleus is present in tetrapods except apes and human. The elongated perikaryon and the dorsoventral dendritic orientation distinctly distinguish these neurons from other cranial motoneurons, the nucleus is found in the lateral part of the reticular formation. The neurons differentiate in situ, they do not migrate from the main abducens nucleus. 4. In the submammalian trigeminal and facial nuclei, two basic neuron types can be distinguished on the basis of their morphology. The first type is larger and accumulates in the rostral part of the trigeminal nucleus. This type innervates the jaw closer muscles. The second type is found in the caudal part of the trigeminal nucleus and in the facial nucleus. These neurons innervate the muscular floor of the mouth and the facial contingent supplies the jaw opener muscle. A very characteristic feature in the axonal trajectory is an initial medial course and a hairpin turn, or dorsal loop, at the lateral aspect of the medial longitudinal fasciculus. In addition to the two types of neurons, there is a third type in the frog trigeminal nucleus. This innervates an orbital muscle.(ABSTRACT TRUNCATED AT 400 WORDS)