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Nature Dec 2021Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases, but the pathways that...
Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases, but the pathways that control these responses remain unclear. Here we define a population of inflammatory group 3 innate lymphoid cells (ILC3s) that infiltrate the CNS in a mouse model of multiple sclerosis. These ILC3s are derived from the circulation, localize in proximity to infiltrating T cells in the CNS, function as antigen-presenting cells that restimulate myelin-specific T cells, and are increased in individuals with multiple sclerosis. Notably, antigen presentation by inflammatory ILC3s is required to promote T cell responses in the CNS and the development of multiple-sclerosis-like disease in mouse models. By contrast, conventional and tissue-resident ILC3s in the periphery do not appear to contribute to disease induction, but instead limit autoimmune T cell responses and prevent multiple-sclerosis-like disease when experimentally targeted to present myelin antigen. Collectively, our data define a population of inflammatory ILC3s that is essential for directly promoting T-cell-dependent neuroinflammation in the CNS and reveal the potential of harnessing peripheral tissue-resident ILC3s for the prevention of autoimmune disease.
Topics: Animals; Antigen-Presenting Cells; Antigens; Encephalomyelitis, Autoimmune, Experimental; Immunity, Innate; Lymphocytes; Mice; Multiple Sclerosis; Neuroinflammatory Diseases; Sclerosis
PubMed: 34853467
DOI: 10.1038/s41586-021-04136-4 -
Cell Reports Jun 2021Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of...
Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rodents. Bulk tissue and single-nucleus expression profiling disclose sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage channels, synaptic signaling, and cell adhesion are deregulated differently by epilepsy across sublayers, whereas neurodegenerative signatures primarily involve superficial cells. Pseudotime analysis of gene expression in single nuclei and in situ validation reveal separated trajectories from health to epilepsy across cell types and identify a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate that sublayer- and cell-type-specific changes associated with selective CA1 neuronal damage contribute to progression of hippocampal sclerosis.
Topics: Animals; Epilepsy; Hippocampus; Humans; Mice; Neurodegenerative Diseases; Neurons; Sclerosis
PubMed: 34107264
DOI: 10.1016/j.celrep.2021.109229 -
Epilepsia Sep 2012The association between hippocampal sclerosis (HS) and epilepsy has been known for almost two centuries. For many years, HS was studied in postmortem series; however,... (Review)
Review
The association between hippocampal sclerosis (HS) and epilepsy has been known for almost two centuries. For many years, HS was studied in postmortem series; however, since the mid-20th century, surgical specimens from temporal lobe resections have provided important new knowledge. HS is the most common pathology underlying drug-resistant mesial temporal lobe epilepsy (MTLE), a syndrome with a characteristic history and seizure semiology. In the early 1990 s, it was recognized that magnetic resonance imaging (MRI) could detect HS. The standard MRI protocol for temporal lobe abnormalities uses coronal slices perpendicular to the long axis of the hippocampus. The MRI features of HS include reduced hippocampal volume, increased signal intensity on T(2)-weighted imaging, and disturbed internal architecture. The histopathologic diagnosis of HS is usually straightforward, with neuronal loss and chronic fibrillary gliosis centered on the pyramidal cell layer. There are several patterns or subtypes of HS recognized from surgical series based on qualitative or quantified assessments of regional neuronal loss. The pathologic changes of HS include granule cell dispersion, mossy fiber sprouting, and alterations to interneurons. There may also be more extensive sclerosis of adjacent structures in the medial temporal lobe, including the amygdala and parahippocampal gyrus. Subtle cortical neuropathologies may accompany HS. The revised classification of dysplasias in epilepsy denotes these as focal cortical dysplasias type IIIa. Sometimes, HS occurs with a second lesion, either in the temporal lobe or extratemporal, most often ipsilateral to the HS. HS on preoperative MRI strongly predicts good seizure outcome following temporal lobe resection (TLR). If adequate MRI shows no structural correlate in patients with MTLE, functional imaging studies are valuable, especially if they are in agreement with ictal electroencephalography (EEG) findings. Focal hypometabolism on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) ipsilateral to the symptomatic temporal lobe predicts a good surgical outcome; the added value of (11) C-Flumazenil-PET (FMZ-PET) and proton magnetic resonance spectroscopy (MRS) is less clear. Surgical methods have evolved, particularly resecting less tissue, aiming to preserve function without compromising seizure outcome. Around two thirds of patients operated for MTLE with HS obtain seizure freedom. However, the best surgical approach to optimize seizure outcome remains controversial.
Topics: Brain; Cadaver; Epilepsy, Temporal Lobe; Hippocampus; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neurosurgical Procedures; Positron-Emission Tomography; Sclerosis
PubMed: 22946718
DOI: 10.1111/j.1528-1167.2012.03610.x -
Pharmacological Reports : PR 2013Hippocampal sclerosis (HS) is considered one of the major pathogenic factors of drug-resistant temporal lobe epilepsy. HS is characterized by selective loss of pyramidal... (Review)
Review
Hippocampal sclerosis (HS) is considered one of the major pathogenic factors of drug-resistant temporal lobe epilepsy. HS is characterized by selective loss of pyramidal neurons - especially of sectors CA1 and CA3 of the hippocampus - pathological proliferation of interneuron networks, and severe glia reaction. These changes occur in the course of long-term and complex epileptogenesis. The authors, on the basis of a review of the literature and own experience, present the pathomechanisms leading to hippocampal sclerosis and epileptogenesis, including various morphological and functional elements of this structure of the brain and pharmacological possibilities of preventing these processes.
Topics: Animals; Epilepsy, Temporal Lobe; Hippocampus; Humans; Sclerosis
PubMed: 23950578
DOI: 10.1016/s1734-1140(13)71033-8 -
Arquivos de Neuro-psiquiatria Jun 2020
Topics: Hippocampus; Humans; Paracoccidioidomycosis; Sclerosis
PubMed: 32609191
DOI: 10.1590/0004-282X20200015 -
The Indian Journal of Medical Research Jun 2019
Topics: Female; Humans; India; Mediastinitis; Middle Aged; Sclerosis
PubMed: 31496535
DOI: 10.4103/ijmr.IJMR_1364_17 -
Current Neurology and Neuroscience... Jan 2016Neurocysticercosis (NCC) is the most common helminthic infection of the nervous system and a frequent cause of reactive seizures and epilepsy worldwide. In many cases,... (Review)
Review
Neurocysticercosis (NCC) is the most common helminthic infection of the nervous system and a frequent cause of reactive seizures and epilepsy worldwide. In many cases, multiple episodes of focal seizures related to an identifiable parenchymal brain cyst (and likely attributable to local damage) continue for years after the cyst resolves. However, cases where seizure semiology, interictal EEG abnormalities, and parasites location do not correlate raise concerns about the causal relationship between NCC and either reactive seizures or epilepsy, as well as the epileptogenic potential of parasites. Neurosurgical series of patients with intractable epilepsy and cross-sectional population-based studies have shown a robust association between NCC and hippocampal sclerosis (HS), which might contribute to the above-referred inconsistencies. Current information does not allow to define whether in patients with NCC, HS could result from recurrent seizure activity from a local or distant focus or from chronic recurrent inflammation. In either case, HS may become the pathological substrate of subsequent mesial temporal lobe epilepsy (MTLE). Longitudinal clinical- and population-based cohort studies are needed to evaluate the causal relationship between NCC and HS and to characterize this association with the occurrence of MTLE. If a cause-and-effect relationship between NCC and HS is demonstrated, NCC patients could be assessed to examine neuronal mechanisms of hippocampal epileptogenesis in comparison with animal models, to identify biomarkers of hippocampal epileptogenesis, and to develop novel interventions to prevent epilepsy in NCC and perhaps in other forms of acquired epilepsy.
Topics: Animals; Epilepsy; Hippocampus; Humans; Neurocysticercosis; Sclerosis; Seizures
PubMed: 26659841
DOI: 10.1007/s11910-015-0601-x -
La Revue Du Praticien May 2013IgG4-related disease is an emerging pathological condition characterized by one or several fibrosing and inflammatory organ involvements. Histological findings are...
IgG4-related disease is an emerging pathological condition characterized by one or several fibrosing and inflammatory organ involvements. Histological findings are typical and associate storiform fibrosis with polyclonal lymphocytic and plasma-cell infiltrate, with predominant IgG4-expressing plasma cells. Sclerosing lymphoplasmocytic pancreatitis, or type 1 auto-immune pancreatitis, and other organ involvements have been reported: sclerosing cholangitis, sialadenitis, dacryoadenitis, retroperitoneal fibrosis, aortitis, interstitial nephritis, polyadenopathy and inflammatory pseudo-tumors. Serum IgG4 level is elevated in most of patients, but the histological documentation remain necessary for the diagnosis. Dramatic response to steroids is usual but relapses are frequent.
Topics: Autoimmune Diseases; Cholangitis; Humans; Immunoglobulin G; Models, Biological; Nephritis, Interstitial; Pancreatitis; Retroperitoneal Fibrosis; Sclerosis; Sialadenitis
PubMed: 23789481
DOI: No ID Found -
International Journal of Gynecological... Jul 2018To determine if vestibulovaginal sclerosis and lichen sclerosus (LS) are 2 distinct entities. Biopsies obtained from the vagina or vulvar vestibule that contained...
To determine if vestibulovaginal sclerosis and lichen sclerosus (LS) are 2 distinct entities. Biopsies obtained from the vagina or vulvar vestibule that contained abnormal subepithelial collagen were reviewed. Cases were categorized either as LS or vestibulovaginal sclerosis based on presence or absence of basal layer degeneration and lymphocytic infiltrate. Clinical data collected included examination findings, biopsy site and indication, previous vulvovaginal surgery, medications at time of biopsy, vulvar LS, treatment, and response. There were 15 cases with a mean age of 62 yr (range: 32-86 yr); 12 (80%) specimens were from vestibule and 3 from vagina. Nine cases were categorized as LS because of lymphocytic infiltrate in combination with basal layer degeneration, of these 8 had LS elsewhere on vulvar skin. Six cases were classified as vestibulovaginal sclerosis and had an absent or sparse lymphocytic infiltrate and essentially normal epithelium; none of these had vulvar LS. While vestibulovaginal sclerosis and lichen sclerosus are distinguishable clinically and histopathologically, further studies are needed to determine if vestibulovaginal sclerosis is a subset of LS or a different condition.
Topics: Adult; Aged; Aged, 80 and over; Collagen; Female; Humans; Middle Aged; Sclerosis; Vagina; Vaginal Diseases; Vulva; Vulvar Lichen Sclerosus
PubMed: 29194107
DOI: 10.1097/PGP.0000000000000441 -
Epilepsia Open Aug 2022Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults, and hippocampal sclerosis (HS) is a frequent histopathological feature in... (Review)
Review
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults, and hippocampal sclerosis (HS) is a frequent histopathological feature in patients with MTLE. Pharmacoresistance is present in at least one-third of patients with MTLE with HS (MTLE+HS). Several hypotheses have been proposed to explain the mechanisms of pharmacoresistance in epilepsy, including the effect of genetic and molecular factors. In recent years, the increased knowledge generated by high-throughput omic technologies has significantly improved the power of molecular genetic studies to discover new mechanisms leading to disease and response to treatment. In this review, we present and discuss the contribution of different omic modalities to understand the basic mechanisms determining pharmacoresistance in patients with MTLE+HS. We provide an overview and a critical discussion of the findings, limitations, new approaches, and future directions of these studies to improve the understanding of pharmacoresistance in MTLE+HS. However, it is important to point out that, as with other complex traits, pharmacoresistance to anti-seizure medications is likely a multifactorial condition in which gene-gene and gene-environment interactions play an important role. Thus, studies using multidimensional approaches are more likely to unravel these intricate biological processes.
Topics: Adult; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Humans; Mental Disorders; Sclerosis
PubMed: 34486831
DOI: 10.1002/epi4.12536