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Science Translational Medicine Sep 2023Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Although the events leading to initial tau misfolding and...
Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Although the events leading to initial tau misfolding and subsequent tau spreading in patient brains are largely unknown, traumatic brain injury (TBI) may be a risk factor for tau-mediated neurodegeneration. Using a repetitive TBI (rTBI) paradigm, we report that rTBI induced somatic accumulation of phosphorylated and misfolded tau, as well as neurodegeneration across multiple brain areas in 7-month-old tau transgenic PS19 mice but not wild-type (WT) mice. rTBI accelerated somatic tau pathology in younger PS19 mice and WT mice only after inoculation with tau preformed fibrils and AD brain-derived pathological tau (AD-tau), respectively, suggesting that tau seeds are needed for rTBI-induced somatic tau pathology. rTBI further disrupted axonal microtubules and induced punctate tau and TAR DNA binding protein 43 (TDP-43) pathology in the optic tracts of WT mice. These changes in the optic tract were associated with a decline of visual function. Treatment with a brain-penetrant microtubule-stabilizing molecule reduced rTBI-induced tau, TDP-43 pathogenesis, and neurodegeneration in the optic tract as well as visual dysfunction. Treatment with the microtubule stabilizer also alleviated rTBI-induced tau pathology in the cortices of AD-tau-inoculated WT mice. These results indicate that rTBI facilitates abnormal microtubule organization, pathological tau formation, and neurodegeneration and suggest microtubule stabilization as a potential therapeutic avenue for TBI-induced neurodegeneration.
Topics: Animals; Mice; Brain Injuries, Traumatic; Microtubules; DNA-Binding Proteins; Brain; Alzheimer Disease; Disease Models, Animal; Excipients; Mice, Transgenic
PubMed: 37703352
DOI: 10.1126/scitranslmed.abo6889 -
Progress in Brain Research 2022This chapter provides a review of early studies into the neural substrate for optokinetic-vestibular responses. Properties and connections of retinal and brainstem... (Review)
Review
This chapter provides a review of early studies into the neural substrate for optokinetic-vestibular responses. Properties and connections of retinal and brainstem neurons contributing to optokinetic responses in the afoveate rabbit are summarized. Electrophysiological and lesion studies provide support for confluence of optokinetic and vestibular signals in the vestibular nucleus to provide the brain's estimate of self-rotation. Evidence for optokinetic-vestibular symbiosis in humans comes from the observation that individuals who have lost vestibular function show no optokinetic after-nystagmus in darkness, following full-field stimulus motion. An anatomical scheme for brainstem elaboration of optokinetic responses is proposed and cerebellar contributions are reviewed.
PubMed: 35074057
DOI: 10.1016/bs.pbr.2021.10.012 -
Journal Francais D'ophtalmologie Jan 2022Ocular paraneoplastic syndromes are rare conditions that can affect any part of the eye at any age. Thus, every ophthalmologist should be familiar with their management,... (Review)
Review
Ocular paraneoplastic syndromes are rare conditions that can affect any part of the eye at any age. Thus, every ophthalmologist should be familiar with their management, as some of them may reveal severe, life-threatening conditions. These consist overwhelmingly of neuro-ophthalmological manifestations, affecting the optic nerve (paraneoplastic optic neuritis), retina (paraneoplastic retinopathy) or neurological pathways generating eye movements (saccadic intrusion, oculomotor palsy, nystagmus...); occasionally, they involve the anterior segment, orbit or uveal tract. As some of these manifestations appear to be quite common and non-specific, any systemic or especially neurologic comorbidities should increase suspicion. Treatment relies first on oncologic management, and then often more targeted therapy for the associated immune involvement.
Topics: Autoantibodies; Humans; Ocular Motility Disorders; Optic Neuritis; Paraneoplastic Syndromes, Ocular; Retinal Diseases
PubMed: 34598825
DOI: 10.1016/j.jfo.2021.08.002 -
Neuroimaging Clinics of North America Feb 2022Chemoradiation for head and neck cancer is associated with a variety of early and late complications. Toxicities may affect the aero-digestive tract (mucositis, salivary... (Review)
Review
Chemoradiation for head and neck cancer is associated with a variety of early and late complications. Toxicities may affect the aero-digestive tract (mucositis, salivary gland injury), regional osseous and cartilaginous structures (osteoradionecrosis (ORN) and chondronecrosis), vasculature (progressive radiation vasculopathy and carotid blow out syndromes), and neural structures (optic neuritis, myelitis, and brain injury). These may be difficult to distinguish from tumor recurrence on imaging, and may necessitate the use of advanced MRI and molecular imaging techniques to reach the correct diagnosis. Secondary radiation-induced malignancies include thyroid cancer and a variety of sarcomas that may manifest several years after treatment. Checkpoint inhibitors can cause a variety of adverse immune events, including autoimmune hypophysitis and encephalitis.
Topics: Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Osteoradionecrosis
PubMed: 34809846
DOI: 10.1016/j.nic.2021.08.012 -
Journal of Neuro-ophthalmology : the... Jun 2021Affection of the central nervous system and the eyes is increasingly recognized as manifestations of a SARS-CoV-2 infection (COVID-19). This review aims at summarizing... (Review)
Review
OBJECTIVES
Affection of the central nervous system and the eyes is increasingly recognized as manifestations of a SARS-CoV-2 infection (COVID-19). This review aims at summarizing and discussing recent advances concerning causes and locations of impaired vision because of an infection with SARS-CoV-2.
METHODS
On a literature search through PubMed and ScholarOne, all available publications about COVID-19 patients with impaired vision were retrieved.
RESULTS
Visual impairment in SARS-CoV-2-infected patients may be due to infection of lacrimal glands (dacryoadenitis), conjunctivitis, tonic pupils, vitritis, central retinal artery/venous occlusion, retinitis, retinal bleeding, panuveitis, anterior ischemic optic neuropathy, optic nerve stroke, optic neuritis, optic perineuritis, or occipital ischemic stroke. Visual impairment may be the initial manifestation of SARS-CoV-2.
CONCLUSIONS
This mini review shows that impaired vision may be the initial manifestation of COVID-19, that all sections of the visual tract may be affected and causative for visual impairment in COVID-19 patients, and that SARS-CoV-2 manifests along the visual tract with ischemia, focal infection, and immunological reactions.
Topics: COVID-19; Humans; Incidence; Pandemics; SARS-CoV-2; Vision Disorders
PubMed: 33999887
DOI: 10.1097/WNO.0000000000001273 -
Journal of Neuroimmunology Jun 2022Neuro-sarcoidosis has important ophthalmic and neuro-ophthalmic manifestations. Sarcoidosis most commonly affects the uveal tract (iris, ciliary body, and choroid)...
Neuro-sarcoidosis has important ophthalmic and neuro-ophthalmic manifestations. Sarcoidosis most commonly affects the uveal tract (iris, ciliary body, and choroid) however the optic nerve is commonly involved. Sarcoid related optic neuritis is an important differential diagnosis in optic neuritis especially in atypical presentations. The use of multimodal imaging techniques available in the ophthalmic setting can enable the detection of choroidal or optic nerve granulomas and aid the diagnosis. Efferent manifestations of neuro-sarcoidosis are broad and can range from isolated cranial neuropathies or multiple as well as pupil abnormalities. Currently to date there are no diagnostic framework to assist in the diagnosis of ophthalmic manifestations in neuro-sarcoidosis in the absence of a tissue biopsy.
Topics: Diagnosis, Differential; Granuloma; Humans; Optic Nerve; Optic Neuritis; Sarcoidosis
PubMed: 35405430
DOI: 10.1016/j.jneuroim.2022.577851 -
Clinical & Experimental Optometry Jan 2022Multiple sclerosis (MS) is a neurological inflammatory disorder known to attack the heavily myelinated regions of the nervous system including the optic nerves,... (Review)
Review
Multiple sclerosis (MS) is a neurological inflammatory disorder known to attack the heavily myelinated regions of the nervous system including the optic nerves, cerebellum, brainstem and spinal cord. This review will discuss the clinical manifestations and investigations for MS and other similar neurological inflammatory disorders affecting vision, as well as the effects of MS treatments on vision. Assessment of visual pathways is critical, considering MS can involve multiple components of the visual pathway, including optic nerves, uvea, retina and occipital cortex. Optical coherence tomography is increasingly being recognised as a highly sensitive tool in detecting subclinical optic nerve changes. Magnetic resonance imaging (MRI) is critical in MS diagnosis and in predicting long-term disability. Optic neuritis in MS involves unilateral vision loss, with characteristic pain on eye movement. The visual loss in neuromyelitis optica spectrum disorder tends to be more severe with preferential altitudinal field loss, chiasmal and tract lesions are also more common. Other differential diagnoses include chronic relapsing inflammatory optic neuropathy and giant cell arteritis. Leber's hereditary optic neuropathy affects young males and visual loss tends to be painless and subacute, typically involving both optic nerves. MS lesions in the vestibulocerebellum, brainstem, thalamus and basal ganglia may lead to abnormalities of gaze, saccades, pursuit and nystagmus which can be identified on eye examination. Medial longitudinal fasciculus lesions can cause another frequent presentation of MS, internuclear ophthalmoplegia, with failure of ipsilateral eye adduction and contralateral eye abduction nystagmus. Treatments for MS include high-dose corticosteroids for acute relapses and disease-modifying medications for relapse prevention. These therapies may also have adverse effects on vision, including central serous retinopathy with corticosteroid therapy and macular oedema with fingolimod.
Topics: Humans; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Optic Atrophy, Hereditary, Leber; Optic Nerve; Optic Neuritis; Tomography, Optical Coherence; Vision Disorders
PubMed: 34348598
DOI: 10.1080/08164622.2021.1947745