Functional Implications of Neurotransmitter Segregation

Here, we present and discuss the characteristics and properties of neurotransmitter segregation, a subtype of neurotransmitter cotransmission. We review early evidence of segregation and discuss its properties, such as plasticity, while placing special emphasis on its probable functional implications, either in the central nervous system (CNS) or the autonomic nervous system. Neurotransmitter segregation is a process by which neurons separately route transmitters to independent and distant or to neighboring neuronal processes; it is a plastic phenomenon that changes according to synaptic transmission requirements and is regulated by target-derived signals. Distant neurotransmitter segregation in the CNS has been shown to be related to an autocrine/paracrine function of some neurotransmitters. In retinal amacrine cells, segregation of acetylcholine (ACh) and GABA, and glycine and glutamate to neighboring terminals has been related to the regulation of the firing rate of direction-selective ganglion cells. In the rat superior cervical ganglion, segregation of ACh and GABA to neighboring varicosities shows a heterogeneous regional distribution, which is correlated to a similar regional distribution in transmission strength. We propose that greater segregation of ACh and GABA produces less GABAergic inhibition, strengthening ganglionic transmission. Segregation of ACh and GABA varies in different physiopathological conditions; specifically, segregation increases in acute sympathetic hyperactivity that occurs in cold stress, does not vary in chronic hyperactivity that occurs in hypertension, and rises in early ages of normotensive and hypertensive rats. Given this, we propose that variations in the extent of transmitter segregation may contribute to the alteration of neural activity that occurs in some physiopathological conditions and with age.

Cannabidiol activates neuronal Kv7 channels

Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and found enhancement of flux through heterologously-expressed human Kv7.2/7.3 channels by CBD. Using patch clamp recordings, we found that CBD at low concentrations activates Kv7.2/7.3 channels at subthreshold voltages, with 100 nM CBD producing a doubling of current at -50 mV. CBD shifted the voltage-dependence of channels in the hyperpolarizing direction, producing a shift in the midpoint of activation by about ~-14 mV at 300 nM. CBD also effectively enhanced native M-current in both mouse superior cervical ganglion neurons and rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD seems likely to contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability.

Carcinoma Ex Pleomorphic Adenoma of the Uvula - Case Report

Introduction: Carcinoma Ex Pleomorphic Adenoma (CEPA) results from the malignant transformation of a benign tumor of the Salivary Glands (SG), the Pleomorphic Adenoma (PA). PA is considered the most common salivary tumor with a 5% risk of malignant transformation and its excision is recommended. CEPA is a rare tumor, corresponding to 3.6% of all salivary tumors and 11.6% of all GS carcinomas. About 18% of CEPAs affect minor SG, with the palate being the most common location. The present work serves to describe a case of a CEPA of the Uvula Minor SG (UMSG). Case Report: We present a case report of a 57-year-old patient, with no relevant medical history, referred to the ENT consultation due to the appearance and progressive growth of a painless uvula lesion. The objective ENT examination showed a 15 mm ulcerative-vegetating lesion with apparent origin on the posterior face of the uvula. The lesion was biopsied and histopathological examination identified the presence of a neoplasm of the minor SG, probably NOS adenocarcinoma. The patient underwent Computed Tomography (CT) scan that showed an irregularity of the uvula, with no signs of invasion of the remaining soft palate, without other significant pharyngo-laryngeal changes. The patient underwent partial pharyngectomy and bilateral selective cervical ganglion dissection, and the histopathology of the surgical specimen confirmed that it was an invasive CEPA, the malignant component of the tumor corresponding to a NOS adenocarcinoma of the UMSG. The patient has been followed up in the ENT consultation, with no signs so far of loco-regional recurrence. Discussion/Conclusion: In the presented case, the patient probably developed an undiagnosed PA that had become malignant over time. Given that it is a poor prognosis neoplasm, it’s essential that the ENT specialists are aware of this disease, in order to facilitate and anticipate the diagnosis and treatment as much as possible.

Methods and Applications of Campenot Trichamber Neuronal Cultures for the Study of Neuroinvasive Viruses

The development of compartmentalized neuron culture systems has been invaluable in the study of neuroinvasive viruses, including the alpha herpesviruses Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PRV). This chapter provides updated protocols for assembling and culturing rodent embryonic superior cervical ganglion (SCG) and dorsal root ganglion (DRG) neurons in Campenot trichamber cultures. In addition, we provide several illustrative examples of the types of experiments that are enabled by Campenot cultures: 1. Using fluorescence microscopy to investigate axonal outgrowth/extension through the chambers, and alpha herpesvirus infection, intracellular trafficking, and cell-cell spread via axons. 2. Using correlative fluorescence microscopy and cryo electron tomography to investigate the ultrastructure of virus particles trafficking in axons.

SYNAPTIC RESPONSES OF SUPERIOR CERVICAL GANGLION NEURONS OF RATS WITH EXPERIMENTAL DIABETES MELLITUS

Excitatory postsynaptic potentials (EPSP) were recorded from the superior cervical ganglion neurons (SCG) in the rats with experimental streptozotocininduced diabetes (ESD). EPSP was inducted by electrical stimulation of the cervical sympathetic trunk. It was founded that the average value of the EPSP time constant decay in the rats with ESD was 15% higher. At the same time, the amplitudes of EPSP of SCG neurons and the hexamethonium blocking effect in the rats with ESD on 30th day after streptozotocin injection didn’t differ significantly from those in control rats. This may indicate specific functional disorders associated as with steady-state elevated blood glucose level in rats as SCG neurons nicotinic cholinergic receptors.

Painful ophthalmoplegia due to involvement of cavernous sinus region by malignant neoplasm: report of three cases

Context: Intracranial tumor spread is an infrequent and late manifestation of head and neck cancers. We report three cases of painful ophthalmoplegia due to larynx and parotid neoplastic involvement. Data disclosure was authorized by the patients through an Informed Consent Form. Case reports: A 47-year-old man presents right retro- orbital pain and progressive ophthalmoplegia 5 months after resection of laryngeal spinocellular carcinoma and local radiotherapy. A 44-year-old man, 9 months after excision of spinocellular carcinoma of the larynx and subsequent radiotherapy, presents severe pain and paralysis of the left CN VI. Imaging exams showed involvement of CS. A 67-year-old woman with a tumoral mass in the left preauricular region. Biopsy revealed adenocarcinoma of the parotid gland. After total parotidectomy, the supra-omohyoid cervical ganglion was removed. Patient received radiotherapy for 3 months. Then, she presented a frontal and right temporal headache, more intense in the retro-orbital region. After one month, she developed complete CS syndrome, with the right CN VI being the first to be affected. MRI revealed an irregular enhancement lesion in right CS after contrast administration. All patients died despite treatment. Conclusions: In patients with painful ophthalmoplegia, the most common hypotheses are diabetic neuropathy and Tolosa-Hunt syndrome. CS involvement may be the first evidence of a distant head and neck disease. Despite the poor prognosis, palliative care should be considered.

Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults

The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.

Variations of Foramen Transversarium in Typical Cervical Vertebrae

The cardinal feature of cervical vertebrae is the foramen transversarium, which transmits the vertebral artery, its accompanying vein and a sympathetic plexus from the inferior cervical ganglion. The aim of the present study was to observe the variations in the size and shape and number of foramen transversarium of typical cervical vertebrae. The study material consisted of 176 typical cervical vertebrae of unknown sex and origin, taken from adult dried human bones present in archieve of department of anatomy. The maximum and minimum mean diameters of the foramen transversarium on the right side were 6.54 mm and 5.39 mm respectively. On the left side, the maximum and minimum mean diameters of the foramen transversarium were 6.28 mm and 5.27 mm respectively. The difference of parameters on the right & left side was statistically insignificant. In no case was the foramen transversarium absent though it was asymmetrical in two cervical vertebrae. Accessory foramen transversarium were present in 11 cervical vertebrae which were present bilaterally in 7 and unilaterally in 4 vertebrae (1 right-sided and 3 left-sided). These accessory foramina could be due of remnants of costal element or due to variations in the vertebral vessels. The anatomical knowledge of the variations in the F.T of cervical vertebrae can be of importance to the neurologists, clinicians and radiologists for proper interpretation of X-rays and CT scans. This knowledge can also play an important role in identification of the dead bodies if ante mortem radiographs of the deceased are available for comparison.

First Bite Syndrome: Presentation of a Patient Status-Post Right Carotid Endarterectomy

First bite syndrome (FBS) is a sharp unilateral pain in the vicinity of the angle of the mandible after taking the first bite of a meal that presents typically after surgery in the area of the ipsilateral parapharyngeal space. It is not confirmed what the pathophysiology is that causes this pain, but the proposed mechanism is the iatrogenic damage of sympathetic fibers that extend from the superior cervical ganglion (SCG) to innervate the parotid gland. The presentation of this syndrome has been acknowledged in patients who have undergone head and neck tumor resections, but it has not been documented in the same thorough manner among vascular surgery cases in the parapharyngeal space, possibly because of a higher risk of development in other head and neck surgeries, or to under-reporting of cases. To date, only 5 cases of FBS status post carotid endarterectomy have been documented in the literature. Definitive treatment of FBS has not been established. Some studies have shown improvement with amitriptyline, and carbamazepine as well as botulinum toxin injections. We will present the case of a 75 year old male who developed first bite syndrome after a right carotid endarterectomy with efforts of raising awareness of a potential acute complication of carotid endarterectomy.