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      Quantitative and qualitative evaluation of the hippocampal cytoarchitecture in adult cats with regard to the pathological diagnosis of hippocampal sclerosis

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          Abstract

          Cats are known to be affected by hippocampal sclerosis, potentially causing antiseizure drug(s) resistance. In order to lay the foundation for a standardized, systematic classification and diagnosis of this pathology in cats, this prospective study aimed at evaluating normal reference values of cellular densities and the cytoarchitecture of the feline hippocampus. Three transverse sections (head, body and tail) of each left hippocampus were obtained from 17 non-epileptic cats of different brachycephalic and mesocephalic breeds and age classes (range: 3–17 years). Histological (hematoxylin and eosin, Nissl) and immunohistochemical (NeuN, GFAP) staining was performed to investigate neuron and astroglial cell populations, as well as the layer thickness of the pyramidal cell layer and granule cell layer. Significant differences in neuronal density (in CA2-CA4 and the granule cell layer) and layer thickness (in CA1-CA3 and the granule cell layer) were evidenced throughout the longitudinal hippocampal axis (p<0.05); on the other hand, the astrocyte density did not differ. Moreover, reference ranges were defined for these parameters in the pyramidal cell layer and in the granule cell layer. The findings did not differ according to breed or age. In veterinary medicine these parameters have not been evaluated in cats so far. As surgical treatment may become a therapeutic option for cats with temporal lobe epilepsy, estimating normal values of the hippocampal cytoarchitecture will help in the standardized histopathological examination of resected hippocampal specimens to reach a diagnosis of hippocampal sclerosis.

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          Reduced fear expression after lesions of the ventral hippocampus.

          The hippocampus has a critical role in several fundamental memory operations, including the conditioning of fear to contextual information. We show that the hippocampus is necessary also for unconditioned fear, and that the involved circuitry is at the ventral pole of the hippocampus. Rats with selective hippocampal lesions failed to avoid open arms in an elevated plus-maze and had decreased neuroendocrine stress responses during confinement to a brightly lit chamber. These effects were reproduced by lesions of the ventral half of the hippocampus, but not by damage to the dorsal three-quarters of the hippocampus or the amygdala. Ventral lesions failed to impair contextual fear conditioning or spatial navigation, suggesting that the ventral hippocampus may specifically influence some types of defensive fear-related behavior.
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            International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods.

            Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug-resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well-preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no-HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
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              Mesial temporal lobe epilepsy: what have we learned?

              Mesial temporal lobe epilepsy is the most common form of human epilepsy, and its pathophysiological substrate is usually hippocampal sclerosis, the most common epileptogenic lesion encountered in patients with epilepsy. The disabling seizures associated with mesial temporal lobe epilepsy are typically resistant to antiepileptic drugs but can be abolished in most patients by surgical treatment. Anteromesial temporal resection, therefore, is the most common surgical procedure performed to treat epilepsy, and stereotactically implanted intracerebral electrodes are required in some patients to localize the epileptogenic region. This clinical setting provides a large number of patients for invasive in vivo research with microelectrode and microdialysis techniques and in vitro research following surgical resection on a single epileptic disorder. Consequently, much has now been learned about the fundamental neuronal mechanisms underlying the epileptogenic properties of the human hippocampus in mesial temporal lobe epilepsy. Parallel reiterative studies in patients and animal models of this disorder indicate that enhanced inhibition, in addition to enhanced excitation, underlies the appearance of hypersynchronous neuronal discharges responsible for generating spontaneous seizures. Recent studies have elucidated what may be unique electrophysiological markers of epileptogenicity, which could have valuable diagnostic utility. Although basic research on mesial temporal lobe epilepsy may ultimately suggest novel approaches to treatment and prevention, attention must also be given to maximizing the application of available effective treatments. In particular, the safety and efficacy of surgical therapy has greatly improved in recent years, yet this alternative treatment remains seriously underutilized worldwide. An appropriate increase in referral of patients with this surgically remediable syndrome to epilepsy centers will not only relieve a great many patients of their disabling seizures and reduce the burden of epilepsy but will also provide increased opportunities for invasive research that could ultimately result in even more effective therapies or cures.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ResourcesRole: Validation
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 May 2022
                2022
                : 17
                : 5
                : e0268010
                Affiliations
                [1 ] Department of Veterinary Clinical Sciences, Small Animal Clinic, Justus-Liebig-University, Giessen, Hessen, Germany
                [2 ] Institute of Neuropathology, Justus-Liebig-University, Giessen, Hessen, Germany
                [3 ] Institute for Biomathematics, Justus-Liebig-University, Giessen, Hessen, Germany
                [4 ] Institute for Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University, Giessen, Hessen, Germany
                Nathan S Kline Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-4112-6518
                Article
                PONE-D-22-02448
                10.1371/journal.pone.0268010
                9106214
                35560321
                f3db5cf5-0046-494c-8c0d-40b3a97115ec
                © 2022 Zilli et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 January 2022
                : 20 April 2022
                Page count
                Figures: 10, Tables: 4, Pages: 23
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Brain
                Hippocampus
                Medicine and Health Sciences
                Anatomy
                Brain
                Hippocampus
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Cats
                Biology and Life Sciences
                Zoology
                Animals
                Vertebrates
                Amniotes
                Mammals
                Cats
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Neurons
                Ganglion Cells
                Pyramidal Cells
                Biology and Life Sciences
                Neuroscience
                Cellular Neuroscience
                Neurons
                Ganglion Cells
                Pyramidal Cells
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Nuclear Staining
                Nissl Staining
                Biology and Life Sciences
                Veterinary Science
                Veterinary Medicine
                Veterinary Diagnostics
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Neurons
                Biology and Life Sciences
                Neuroscience
                Cellular Neuroscience
                Neurons
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Surgical Resection
                Biology and Life Sciences
                Anatomy
                Brain
                Hippocampal Formation
                Dentate Gyrus
                Medicine and Health Sciences
                Anatomy
                Brain
                Hippocampal Formation
                Dentate Gyrus
                Custom metadata
                All relevant data are within the paper and its Supporting information files.

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