Coronaviruses and their relationship with multiple sclerosis: is the prevalence of multiple sclerosis going to increase after the Covid-19 pandemia?

The purpose of this review is to examine whether there is a possible (etiological/triggering) relationship between infection with various Coronaviruses, including Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemia, and Multiple Sclerosis (MS), and whether an increase of the prevalence of MS after the current Covid-19 pandemia should be expected, examining new and preexisting data. Although the exact pathogenesis of MS remains unknown, environmental agents seem to greatly influence the onset of the disease, with viruses being the most popular candidate. Existing data support this possible etiological relationship between viruses and MS, and experimental studies show that Coronaviruses can actually induce an MS-like demyelinating disease in animal models. Findings in MS patients could also be compatible with this coronaviral MS hypothesis. More importantly, current data from the Covid-19 pandemia show that SARS-CoV-2 can trigger autoimmunity and possibly induce autoimmune diseases, in the Central Nervous System as well, strengthening the viral hypothesis of MS. If we accept that Coronaviruses can induce MS, it is reasonable to expect an increase in the prevalence of MS after the Covid-19 pandemia. This knowledge is of great importance in order to protect the aging groups that are more vulnerable against autoimmune diseases and MS specifically, and to establish proper vaccination and health policies.

Morphological and morphometric changes in the Purkinje cells of patients with essential tremor.

Essential tremor (ET) is a progressive neurological syndrome characterised by involuntary tremors of the hands or arms, head, jaw and voice. The pathophysiology of ET is not clearly understood yet. However, previous studies have reported several changes in the brain of patients with ET. One of the brain areas extensively investigated is the cerebellum. In the present study, a morphometric analysis of Purkinje cells in patients with ET and ET-plus was performed, and subsequently compared with normal controls using the Golgi silver staining method and 3D neuronal reconstruction. Substantial morphological changes were uncovered in the Purkinje cells of patients with ET compared with normal controls, including a decreased dendritic length and field density, an overall loss of terminal branches and a decreased density of dendritic spines.

Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System.

PURPOSE OF REVIEW: To describe the possible neuroinvasion pathways of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemic. RECENT FINDINGS: We present data regarding the family of Coronaviruses (CoVs) and the central nervous system (CNS), and describe parallels between SARS-CoV-2 and other members of the family, which have been investigated in more depth and combine these findings with the recent advancements regarding SARS-CoV-2. SUMMARY: SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. Τhe olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS.

Purkinje Cells Pathology in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the main causes of dementia in senium and presenium. It is clinically characterized by memory impairment, deterioration of intellectual faculties, and loss of professional skills. The cerebellum is a critical part in the distributed neural circuits participating not only in motor function but also in autonomic, limbic, and cognitive behaviors. In present study, we aim to investigate the morphological changes in the Purkinje cells in different cerebellar regions in AD and to correlate them with the underlying AD pathology. Purkinje cells exhibit significant morphometric alterations in AD and prominently in the anterior lobe which is related to higher cognitive functions. The present study gives new insights into the cerebellar pathology in AD and confirms that Purkinje cells pathology is a key finding in AD brains and that AD is characterized by regional-specific atrophy picked in the anterior cerebellar lobe.

Spinal Alterations of Reil Insula in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that involves numerous cellular and biochemical mechanisms resulting in synaptic alterations and extensive neuronal loss. It is primarily characterized by impairment of memory, associated frequently with mood disorders. Continuous studies have shown that insula may be an important target of AD, but neuropathological alterations have not been described extensively. In the present study, we attempted to describe the morphometric and morphological changes of the spines of Reil insula in AD in comparison with normal aging using a silver impregnation technique. We classified spines into 3 types: (1) long neck, (2) short stubby, and (3) other types; and we measured and correlated the length of them in normal controls and in individuals with AD using ImageJ application. Statistical analysis was based on the Student t test on the basis of 360 cells in SPSS v.17.0, and significance was taken as P < .05.

Mammillary Bodies in Alzheimer's Disease: A Golgi and Electron Microscope Study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by irreversible memory decline, concerning no rarely spatial memory and orientation, alterations of the mood and personality, gradual loss of motor skills, and substantial loss of capacities obtained by previous long education. We attempted to describe the morphological findings of the mammillary bodies in early cases of AD. Samples were processed for electron microscopy and silver impregnation techniques. The nuclei of the mammillary bodies demonstrated a substantial decrease in the neuronal population and marked abbreviation of dendritic arbors. Decrease in spine density and morphological abnormalities of dendritic spines was also seen. Synaptic alterations were prominent. Alzheimer's pathology, such as deposits of amyloid-ß peptide and neurofibrillary degeneration, was minimal. Electron microscopy revealed mitochondrial alterations and fragmentation of Golgi apparatus, associated frequently with synaptic pathology.

Brain capillaries in Alzheimer's disease.

Alzheimer's disease is the most common cause of irreversible dementia, affecting mostly the presenile and senile age, shaping a tragic profile in the epilogue of the life of the suffering people. Due to the severity and the social impact of the disease an ongoing research activity is in climax nowadays, associated with many legal, social, ethical, humanitarian, philosophical and economic considerations. From the neuropathological point of view the disease is characterized by dendritic pathology, loss of synapses and dendritic spines, affecting mostly selective neuronal networks of critical importance for memory and cognition, such as the basal forebrain cholinergic system, the medial temporal regions, the hippocampus and many neocortical association areas. Tau pathology consisted of intracellular accumulation of neurofibrillary tangles of hyperphosphorilated tau protein and accumulation of Aß-peptide's deposits, defined as neuritic plaques, are the principal neuropathological diagnostic criteria of the disease. The neurotoxic properties of the oligomerics of the Aß-peptide and tau mediated neurodegeneration are among the main causative factors of impaired synaptic plasticity, neuronal loss, dendritic alterations and tremendous synaptic loss. The gradual degeneration of the organelles, particularly mitochondria, smooth endoplasmic reticulum and Golgi apparatus, visualized clearly by electron microscopy (EM), emphasize the importance of the oxidative stress and amyloid toxicity in the pathogenetic cascade of the disease. The vascular factor may be an important component of the whole spectrum of the pathogenesis of AD. It is of substantial importance the concept that the structural alterations of the brain capillaries, may contribute in the pathology of AD, given that the disruption of the BBB may induce exacerbation of AD pathology, by promoting inflammation around the blood capillaries and in the neuropile space diffusely. From the morphological point of view, silver impregnation techniques revealed a marked tortuosity of the capillaries in early cases of AD. In addition, the distance between two branch points is longer in capillaries of AD brains, whereas the branch point density as well as the ratio of the branch point density to astrocytic density is substantially decreased in AD in comparison with age matched normal controls. EM revealed, that the most frequent morphological alterations of the brain capillaries in AD consist of thickness, splitting and duplication of the basement membrane, reduction of the length of tight junctions, decrease of the number of tight junctions per vessel length, associated as a rule, with morphological alterations of the mitochondria of the endothelial cells, the pericytes and the perivascular astrocytic processes. The number of the pinocytotic vesicles is substantially increase in the endothelium of the brain capillaries in AD in comparison with age matched normal controls. Endothelial cells play a very important role in the transport systems in the brain. Subsequently, the dysfunction of the endothelial cells and the disruption of the BBB may induce serious impairment in the transport system. The dysfunction of the brain capillaries may result in releasing neurotoxic factors, such as thrombin, pro-inflammatory cytokines, nitric oxide and leukocyte adhesion molecules, and in abnormal regulation of Aß-peptide homeostasis in the brain. The impairment of the brain capillaries in structures of the brain, which are crucial for the homeostatic equilibrium, such as the hypothalamic nuclei, may induce autonomic dysfunction, which usually occur in the advanced stages of AD, affecting dramatically the viability of the patients. Degeneration of the pericytes is also observed emphasizing even more the importance of the vascular factor in AD. Pericytes may serve as integrators, coordinators and effectors of blood-brain barrier structure and maintenance, and play a key role in microvascular stability, capillary density and angiogenesis. The correlation between AD pathology and vascular pathology, at the level of brain capillaries and BBB, raises the rational question, whether the efficient treatment of the vascular factor might be beneficial for the patients who suffer from AD. It is reasonable that any protection of the brain capillaries at the initial stages of the disease might contribute in the abbreviation of the long chain of pathological alteration, which occur following the disruption of the BBB, which serves as the essential interface between the vascular system and the brain.

Age-related dendritic and spinal alterations of pyramidal cells of the human visual cortex.

INTRODUCTION: Normal aging is characterized by deterioration of visual abilities, affecting mainly visual acuity, contrast and wavelength sensitivity. In the present study we attempted to describe the morphological and morphometric alterations of the dendrites and the dendritic spines of the pyramidal cells of the visual cortex during normal aging, in order to approach the visual impairment of aged individuals from a neuropathological point of view. MATERIAL AND METHODS: We studied the visual cortex in 20 brains using the Golgi technique. RESULTS: In pyramidal cells, which represent the majority of cortical neurons, age-related pathology can be observed in cell somata as well as, most importantly, in dendrite number and morphology. The apical dendrites of some pyramidal cells are distorted and tortuous. Horizontal dendritic arborization is also severely decreased. These alterations were more prominent in the corticocortical pyramidal neurons of the 5th layer. CONCLUSIONS: The morphological and morphometric assessment of the dendrites and the dendritic spines in the visual cortex in normal aging revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to visual impairment even in normal aging.

The hypothalamus in Alzheimer's disease: a Golgi and electron microscope study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by irreversible decline of mental faculties, emotional and behavioral changes, loss of motor skills, and dysfunction of autonomic nervous system and disruption of circadian rhythms (CRs). We attempted to describe the morphological findings of the hypothalamus in early cases of AD, focusing our study mostly on the suprachiasmatic nucleus (SCN), the supraoptic nucleus (SON), and the paraventricular nucleus (PVN). Samples were processed for electron microscopy and silver impregnation techniques. The hypothalamic nuclei demonstrated a substantial decrease in the neuronal population, which was particularly prominent in the SCN. Marked abbreviation of dendritic arborization, in association with spinal pathology, was also seen. The SON and PVN demonstrated a substantial number of dystrophic axons and abnormal spines. Alzheimer's pathology, such as deposits of amyloid-ß peptide and neurofibrillary degeneration, was minimal. Electron microscopy revealed mitochondrial alterations in the cell body and the dendritic branches. The morphological alterations of the hypothalamic nuclei in early cases of AD may be related to the gradual alteration of CRs and the instability of autonomic regulation.

Staining of dead neurons by the Golgi method in autopsy material.

Golgi silver impregnation techniques remain ideal methods for the visualization of the neurons as a whole in formalin fixed brains and paraffin sections, enabling to obtain insight into the morphological and morphometric characters of the dendritic arbor, and the estimation of the morphology of the spines and the spinal density, since they delineate the profile of nerve cells with unique clarity and precision. In addition, the Golgi technique enables the study of the topographic relationships between neurons and neuronal circuits in normal conditions, and the following of the spatiotemporal morphological alterations occurring during degenerative processes. The Golgi technique has undergone many modifications in order to be enhanced and to obtain the optimal and maximal visualization of neurons and neuronal processes, the minimal precipitations, the abbreviation of the time required for the procedure, enabling the accurate study and description of specific structures of the brain. In the visualization of the sequential stages of the neuronal degeneration and death, the Golgi method plays a prominent role in the visualization of degenerating axons and dendrites, synaptic "boutons," and axonal terminals and organelles of the cell body. In addition, new versions of the techniques increases the capacity of precise observation of the neurofibrillary degeneration, the proliferation of astrocytes, the activation of the microglia, and the morphology of capillaries in autopsy material of debilitating diseases of the central nervous system.

Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder, causing a progressive decline of intellectual faculties, impairment of behavior and social performance, and impairment of speech eloquence, associated with various neurological manifestations based on a variable neuropathological background. Edinger-Westphal nucleus is a selective target of Alzheimer pathology early in the course of the disease. We attempted to determine the morphological alterations of the dendrites and the dendritic spines in Edinger-Westphal nucleus of 7 cases that fulfilled the diagnostic criteria for Alzheimer's disease. For the histological study, we applied (a) routine neuropathological techniques and (b) rapid Golgi method. We proceeded to 3D neuronal reconstruction for the estimation of dendritic and spinal changes in Alzheimer's disease. The morphological and morphometric analysis revealed a substantial neuronal loss and synaptic alterations in Edinger-Westphal nucleus in all the cases of Alzheimer's disease. Distal dendritic branches are prominently affected. The neuronal loss and alteration of the spines in Edinger-Westphal nucleus in Alzheimer's disease may be related to the exaggerated pupillary reaction to cholinergic antagonists. Furthermore, the vulnerability of distal branches to Alzheimer's disease might be related to neuroplasticity impairment.

The fine structure of ependymomas.

Electron microscopy is a useful diagnostic technique in order to confirm or establish a definitive diagnosis in brain tumors that may have an atypical histological pattern, which requires a concrete diagnosis. In ependymomas, electron microscopy reveals morphological characters that have a pathognomonic diagnostic value, therefore allowing a definitive diagnosis. The main fine structural criteria of ependymomas consist of the numerous microvilli and cilia, which are incorporated in the cell body or extended freely in the intracellular space; the centriole or blepharoplast, which is located in the basis of the cilia; the large number of the fragmented microtubules in the perikaryon and the cellular processes (any small cellular projection into the neutrophil or intracellular space); the junctional apparatus between the cells, such as zonula adherens, zonula occludens and puncta adherentia; the basement membrane-like structure, seen in papillary ependymomas and ependymomas of the filum terminale; and the elongated cells in the loose intracellular space, commonly seen in myxopapillary ependymomas.

Golgi apparatus and protein trafficking in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive degeneration of the brain, inducing memory decline, inability in learning, and behavioral alterations, resulting progressively in a marked deterioration of all mental activities and eventually a vegetative state. The main causative factor, however, is still unclear. The implication of amyloid-ß, AßPP, tau protein, the selective loss of neurons, the alteration of the synapses, the cytoskeletal changes, and the morphological alterations of the brain capillaries contribute substantially to the pathogenetic profile of the disease, without sufficiently enlightening the initial steps of the pathological procedures. The ultrastructure of the neuronal organelles as well as histochemical studies revealed substantial alterations, primarily concerning mitochondria. In this study, the morphological and morphometric alterations of the Golgi apparatus (GA) are described in the Purkinje cells of the cerebellum in twenty AD brains, studied with electron microscopy. As it is well established, GA has a very important role to play in many procedures such as glycosylation, sulfation, and proteolysis of protein systems, which are synthesized in the endoplasmic reticulum of nerve cells and glia. GA may also play a crucial role in protein trafficking and in misfolding of protein aggregates. In addition, the hyperphosphorylation of tau protein is closely related with the pathology of GA. In AD cases, described in this study, an obvious fragmentation of the cisternae of GA was observed in the Purkinje cells of the vermis and the cerebellar hemispheres. This alteration of GA may be associated with alterations of microtubules, impaired protein trafficking, and dendritic, spinal, and synaptic pathology, since protein trafficking plays an essential role in the three dimensional organization of the dendritic arbor and in the integrity of the synaptic components.

Dendritic and spinal pathology of the Purkinje cells from the human cerebellar vermis in Alzheimer's disease.

BACKGROUND: Alzheimer's disease constitutes one of the main causes of dementia. It is clinically characterized by memory impairment, deterioration of intellectual faculties and loss of professional skills. Furthermore changes in equilibrium and limb coordination are clinically demonstrable in persons with Alzheimer's disease. In the present study we tried to figure out possible changes of the Purkinje cells in Alzheimer's disease brains. SUBJECTS AND METHODS: We studied the Purkinje cells from the vermis of the cerebellum in 5 Alzheimer' disease brains Golgi technique. RESULTS: In the Purkinje cells from the inferior surface of the cerebellar hemispheres severe dendritic and spinal pathology consisting of loss of distal dendritic segments and alterations of dendritic spine morphology can be noticed in Alzheimer's disease brains. CONCLUSIONS: The morphological and morphometric estimation of the dendrites and the dendritic spines of the Purkinje cells from the inferior surface of the cerebellar hemispheres in Alzheimer's disease brains revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to cognitive impairment and motor deficits in Alzheimer's disease.

Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).

Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art.

Glutamate receptors in human caudate nucleus in normal aging and Alzheimer's disease.

Neostriatum is one of the brain areas that are not primarily affected in Alzheimer's disease, according to classic regard of the disease. However, recent data emphasize the involvement of neostriatum, especially the head of the caudate nucleus, in the emergence of characteristic symptoms of the disease. Glutamatergic neurotransmission is a key component of striatal pathways. The present study is focused on glutamate receptors of striatal neurons on human caudate nucleus in normal aging and Alzheimer's disease. Immunohistochemical studies were carried out for N-methyl-D-aspartate receptor subunit 1 (NMDAR1), α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit 2 (GluR2) and metabotropic glutamate receptor 5 (mGluR5). Ionotropic receptors (NMDAR1 and GluR2) were found to be expressed by 82% - 93% of striatal neurons with no significant alterations in aging and Alzheimer's disease. On the other hand, metabotropic receptor mGluR5 was found to be expressed by just 40% of striatal neurons in young individuals, with significant intensity variations among the neurons. This percent was increased in elderly individuals and Alzheimer's disease patients to 80% and 92% of striatal neurons, respectively. The up-regulation of mGluR5 both in normal aging and Alzheimer's disease is possibly associated with reorganization of neuronal connections, indicates the complexity of this receptor function and renders quite unpredictable the intervention and treatment of dementia with mGluR5 inhibitors or modulators.

Dendritic, axonal, and spinal pathology of the Purkinje cells and the neurons of the dentate nucleus after long-term phenytoin administration: a case report.

Phenytoin is a commonly prescribed anticonvulsant drug; however, there is evidence that long-term administration is related to cerebellar ataxia, cerebellar atrophy, loss of Purkinje cells, and hyperplasia of Bergman glia cells. The aim of the present study was to detect and describe any possible alterations of the Purkinje cells, and neurons of the dentate nucleus, as those can be seen with the use of silver impregnation techniques, such as Golgi and Nauta method. The study was performed on a 7-year-old boy who was under phenytoin treatment for more than 3.5 years and had clinical manifestations of cerebellar ataxia. Golgi silver impregnation technique revealed substantial loss of dendritic spines and tertiary dendritic branches, both on the Purkinje cells and the neurons of the dentate nucleus, whereas the Nauta method demonstrated swollen and degenerated axons of Purkinje cells.

The vascular factor in Alzheimer's disease: a study in Golgi technique and electron microscopy.

Although the etiopathological background of Alzheimer's disease (AD) is mostly associated with the deposition of Αß-peptide, the hyperphosphorylation of τ protein, the synaptic pathology and the mitochondrial alterations, the vascular factor may play substantial role in plotting the multifactorial pattern of the disease. We attempted to study the blood capillaries in the hippocampus, the acoustic, the visual and the parietal cortex in twelve early cases of Alzheimer's disease. Samples were processed for Golgi silver impregnation technique and electron microscopy. The morphological findings were compared with normal controls. The study of the brain capillaries in cases of AD, revealed numerous fusiform dilatations, tortuosities, abnormal branching and fusion, though the morphometric estimation revealed a decrease of the number of capillaries per mm(3) in comparison with normal control brains. The ultrastructural study revealed mitochondrial abnormalities in the endothelial cells of a substantial number of capillaries and marked degeneration of the pericytes. Perivascular microglial proliferation was also prominent in the hippocampus and the parietal lobe. Our findings both in Golgi staining and electron microscopy plead in favor of the essential role that the microvascular alterations may play in the broad pathogenetic spectrum of AD.

Mitochondria are related to synaptic pathology in Alzheimer's disease.

Morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer's disease, been associated with oxidative stress and Aß-peptide-induced toxicity. We proceeded to estimation of mitochondria on electron micrographs of autopsy specimens of Alzheimer's disease. We found substantial morphological and morphometric changes of the mitochondria in the neurons of the hippocampus, the neocortex, the cerebellar cortex, the thalamus, the globus pallidus, the red nucleus, the locus coeruleus, and the climbing fibers. The alterations consisted of considerable changes of the cristae, accumulation of osmiophilic material, and modification of the shape and size. Mitochondrial alterations were prominent in neurons, which showed a depletion of dendritic spines and loss of dendritic branches. Mitochondrial alterations are not related with the accumulation of amyloid deposits, but are prominent whenever fragmentation of the Golgi apparatus exists. Morphometric analysis showed also that mitochondria are significantly reduced in neurons, which demonstrated synaptic pathology.