Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged （4-month-old） or elderly （7-month-old） senescence-accelerated mouse prone 8 （SAMP8） mice. When the middle-aged mice reached 8 months （middle-aged group 1） or 11 months （middle-aged group 2）, and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus （Nissl staining and acetylcholinesterase histochemistry） and basal forebrain （choline acetyltrans-ferase immunohistochemistry）. In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extraction should be avoided in these populations.

Automated Segmentation of the Brainstem,Cranial Nerves and Vessels for Trigeminal Neuralgia and Hemifacial Spasm

Accurate localization of cranial nerves and responsible blood vessels is important for diagnosing trigeminal neuralgia(TN)and hemifacial spasm(HFS).Manual delineation of the nerves and vessels on medical images is time-consuming and labor-intensive.Due to the development of convolutional neural networks(CNNs),the performance of medical image segmentation has been improved.In this work,we investigate the plans for automated segmentation of cranial nerves and responsible vessels for TN and HFS,which has not been comprehensively studied before.Different inputs are given to the CNN to find the best training configuration of segmenting trigeminal nerves,facial nerves,responsible vessels and brainstem,including the image modality and the number of segmentation targets.According to multiple experiments with seven training plans,we suggest training with the combination of three-dimensional fast imaging employing steady-state acquisition(3D-FIESTA)and three-dimensional time-of-flight magnetic resonance angiography(3DTOF-MRA),and separate segmentation of cranial nerves and vessels.

Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor regulate the interaction between astrocytes and Schwann cells at the trigeminal root entry zone

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes.Its special anatomical and physiological structure renders it susceptible to nerve injury.The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone.This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions.Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor.In monoculture,glial cell line-derived neurotrophic factor promoted the migration of Schwann cells,but it did not have effects on the migration of astrocytes.In the co-culture system,glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells.Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes.However,in the co-culture system,brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree.These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone.This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Gene expression microarray analysis of the spinal trigeminal nucleus in a rat model of migraine with aura

Cortical spreading depression can trigger migraine with aura and activate the trigeminal vascular system. To examine gene expression profiles in the spinal trigeminal nucleus in rats following cortical spreading depression-induced migraine with aura, a rat model was established by injection of 1 M potassium chloride, which induced cortical spreading depression. DNA microarray analysis revealed that, compared with the control group, the cortical spreading depression group showed seven upregulated genes-myosin heavy chain 1/2, myosin light chain 1, myosin light chain （phosphorylatable, fast skeletal muscle）, actin alpha 1, homeobox B8, carbonic anhydrase 3 and an unknown gene. Two genes were downregulated-RGD1563441 and an unknown gene. Real-time quantitative reverse transcription-PCR and bioinformatics analysis indicated that these genes are involved in motility, cell migration, CO2/nitric oxide homeostasis and signal transduction.

Shrinkage of ipsilateral taste buds and hyperplasia of contralateral taste buds following chorda tympani nerve transection

The morphological changes that occur in the taste buds after denervation are not well under- stood in rats, especially in the contralateral tongue epithelium. In this study, we investigated the time course of morphological changes in the taste buds following unilateral nerve transection. The role of the trigeminal component of the lingual nerve in maintaining the structural integrity of the taste buds was also examined. Twenty-four Sprague-Dawley rats were randomly divided into three groups： control, unilateral chorda tympani nerve transection and unilateral chorda tympani nerve transection ＋ lingual nerve transection. Rats were allowed up to 42 days of re- covery before being euthanized. The taste buds were visualized using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell numbers were quantified and compared among groups. No significant difference was detected between the chorda tympani nerve transection and chorda tympani nerve transection ＋ lingual nerve transection groups. Taste bud counts, volumes and taste receptor cell numbers on the ipsilateral side all decreased significantly compared with control. On the contralateral side, the number of taste buds remained unchanged over time, but they were larger, and taste receptor cells were more numerous postoperatively. There was no evidence for a role of the trigeminal branch of the lingual nerve in maintaining the structural integrity of the anterior taste buds.

Distant metastasis of hepatocellular carcinoma to Meckel’s cave and cranial nerves:A case report and review of literature

BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma(HCC),and most patients die of liver failure attributed to the tumor supplanting the liver.Conversely,the brain is a less common metastatic site.CASE SUMMARY We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus,Meckel’s cave,and the petrous bone involving multiple cranial nerves in an 82-year-old woman.At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(MRI)revealed multiple HCC nodules in both right and left lobes.Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC.Molecular targeted therapy with Lenvatinib(8 mg/d for 94 d,per os)and Ramucirumab(340 mg/d and 320 mg/d,two times by intravenous injection)were administered for 4 mo,resulting in progression of the disease.Three months after the start of molecular target therapy,the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye,indicating disturbances in the right trigeminal and abducens nerves.Brain MRI disclosed a mass involving the cavernous sinus,Meckel’s cave and the petrous bone.Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s cave.CONCLUSION The diagnosis of metastatic HCC to the cavernous sinus,Meckel’s cave,and the petrous bone was made based on neurological findings and imaging studies including MRI,but not on histological examinations.Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Gabapentin inhibits central sensitization during migraine

Peripheral and central sensitizations are phenomena that occur during migraine. The role of gabapentin, a migraine preventive drug, on central sensitization remains unclear. In this study, a rat model of migraine was established by electrical stimulation of the trigeminal ganglion, and the animals were given intragastric gabapentin. Changes in amino acid content in the cerebrospinal fluid and protein kinase C membrane translocation in the spinal trigeminal nucleus were examined to clarify the mechanisms underlying the efficacy of gabapentin in the treatment of central sensiti- zation during migraine. Electrophysiology, liquid chromatography-mass spectrometry and western blot analysis results revealed that gabapentin reduces neuronal excitability in the spinal nucleus in the trigeminal nerve, decreases excitatory amino acid content and inhibits the activation of protein kinase C. This provides evidence that excitatory amino acids and protein kinase C are involved in the formation and maintenance of central sensitization during migraine. Gabapentin inhibits mi- graine by reducing excitatory amino acid content in the cerebrospinal fluid and inhibiting protein kinase C activation.

Two Cases of Severe Dementia Showing Dramatic Improvement after Denture Placement

Severe dementia, including Alzheimer’s disease, is intractable and progressive. The purpose of this study was to document the improvement observed in two cases of severe dementia after denture placement. The subjects, two women in their 70s with severe dementia, were diagnosed with Alzheimer’s disease by the medical doctors in charge of their cases. In the first case, the subject’s symptoms included severe disorientation, impaired communication, and a tendency to wander. Two weeks after a lower complete denture placement, she was able to greet others. Five weeks later, she was able to communicate and precisely read an analog clock. Her condition continued to improve for at least 3 months. In the second case, the subject’s mouth was always open. She was bedridden in a vegetative state and hardly moved, talked, or laughed;it was impossible to communicate with her. Only a few seconds after an upper complete denture placement, she started to talk, albeit unintelligibly. Two weeks after a lower complete denture placement, she could communicate normally, laugh, and walk without help. Although the underlying mechanism has not yet been clarified, the author hypothesizes that positive signals from the oral area are transferred to the brain as positive stimulation via the trigeminal nerve, the largest cranial nerve.

Odontogenic Herpes Zoster Infection: A Case Report and Review

Herpes zoster is a commonly encountered entity of which all clinicians should be aware. The diagnosis is most often considered and made based on a characteristic vesicular rash that presents in a unilateral dermatomal distribution and is usually accompanied by a painful neuritis. Not uncommonly, the pain presents a few days before the rash becomes evident and may even occur without the rash appearing. When this happens patients may be subject to further diagnostic testing seeking alternative diagnoses, as herpes zoster is known to mimic a variety of other non-cutaneous organ system entities. Although the thoracic and lumbar dermatomes are the affected most frequently, in approximately one-fifth of cases the cranial nerves are involved either singularly or in combination. Trigeminal nerve zoster is of particular concern as it poses a risk of developing into zoster ophthalmicus with subsequent keratitis and uveitis resulting in permanent vision impairment. Involvement of the second (maxillary) and third (mandibular) branches of this 5th cranial nerve are less common and may present with signs and symptoms of a primary dental process. The infrequency and unfamiliarity of herpes zoster odontogenic manifestations can lead to unnecessary investigation and treatment. Apropos such a case we review the epidemiology, pathophysiology, signs, and symptoms of odontogenic herpes zoster.

Percutaneous microballoon compression for trigeminal neuralgia

Background Percutaneous microballoon compression （PMC） for trigeminal neuralgia is an important therapeutic method. The aim of this study was to review the effects of PMC for trigeminal neuralgia in 276 patients. Methods From December 2000 to May 2003, 276 patients with trigeminal neuralgia were treated with PMC. The course of the disease ranged from 3 months to 38 years. Under the guidance of C-arm X-ray, 14# needle was placed into the foramen ovale using the classical Hakanson＇s technique. Fogarty balloon catheter was navigated into the Meckel＇s cave tenderly. A small amount of Omnipaque was slowly injected to inflate the balloon and compress the trigeminal ganglion for 3 to10 minutes. Results A total of 290 PMC were performed on the 276 patients. Among them, 252 had immediate relief from pain. The patients were followed up for a mean of 18.7 months （range, 4 to 32）, 14 of them had a recurrence. Of the 14 patients, 12 were re-operated with PMC, and the pain was all controlled successfully. Conclusions PMC is an effective and technically simple method for trigeminal neuralgia. For older patients with trigeminal neuralgia, it may be the first choice.

A new classification of nevus of Ota

Background The nevus of Ota, is a common benign pigmentary dermatosis, mainly involve innervation area of first and second branch of trigeminal nerve. The classification of nevus of Ota was proposed by Tanino, based on 26 cases of nevus of Ota from 1937 to 1940. Studies about its classification are rarely seen in last 70 years, while it is still practical today.