scholarly journals Dengue infection in mice inoculated by the intracerebral route: neuropathological effects and identification of target cells for virus replication

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
J. F. S. Amorim ◽  
A. S. Azevedo ◽  
S. M. Costa ◽  
G. F. Trindade ◽  
C. A. Basílio-de-Oliveira ◽  
...  
Keyword(s):  
Dengue Infection ◽  
Clinical Manifestations ◽  
Target Cells ◽  
Histopathological Analysis ◽  
Mice Model ◽  
Pia Mater ◽  
Neurological Morbidity ◽  
Life Threatening ◽  
The Central Nervous System ◽  
The Brain

AbstractDengue is an important arboviral infection, causing a broad range symptom that varies from life-threatening mild illness to severe clinical manifestations. Recent studies reported the impairment of the central nervous system (CNS) after dengue infection, a characteristic previously considered as atypical and underreported. However, little is known about the neuropathology associated to dengue. Since animal models are important tools for helping to understand the dengue pathogenesis, including neurological damages, the aim of this work was to investigate the effects of intracerebral inoculation of a neuroadapted dengue serotype 2 virus (DENV2) in immunocompetent BALB/c mice, mimicking some aspects of the viral encephalitis. Mice presented neurological morbidity after the 7th day post infection. At the same time, histopathological analysis revealed that DENV2 led to damages in the CNS, such as hemorrhage, reactive gliosis, hyperplastic and hypertrophied microglia, astrocyte proliferation, Purkinje neurons retraction and cellular infiltration around vessels in the pia mater and in neuropil. Viral tropism and replication were detected in resident cells of the brain and cerebellum, such as neurons, astrocyte, microglia and oligodendrocytes. Results suggest that this classical mice model might be useful for analyzing the neurotropic effect of DENV with similarities to what occurs in human.

Effects of CSF Properties on Brain Response Under Impact Loading

2009 ◽  
Author(s):  
M. S. Chafi ◽  
V. Dirisala ◽  
G. Karami ◽  
M. Ziejewski
Keyword(s):  
Human Head ◽  
Brain Response ◽  
Pia Mater ◽  
Mechanical Shocks ◽  
The Central Nervous System ◽  
Simultaneous Loading ◽  
The Impact ◽  
Impact Experiments ◽  
The Brain

In the central nervous system, the subarachnoid space is the interval between the arachnoid membrane and the pia mater. It is filled with a clear, watery liquid called cerebrospinal fluid (CSF). The CSF buffers the brain against mechanical shocks and creates buoyancy to protect it from the forces of gravity. The relative motion of the brain due to a simultaneous loading is caused because the skull and brain have different densities and the CSF surrounds the brain. The impact experiments are usually carried out on cadavers with no CSF included because of the autolysis. Even in the cadaveric head impact experiments by Hardy et al. [1], where the specimens are repressurized using artificial CSF, this is not known how far this can replicate the real functionality of CSF. With such motivation, a special interest lies on how to model this feature in a finite element (FE) modeling of the human head because it is questionable if one uses in vivo CSF properties (i.e. bulk modulus of 2.19 GPa) to validate a FE human head against cadaveric experimental data.

scholarly journals III. Contributions to the anatomy of the central nervous system in vertebrated animals. Part I.—Ichthyopsida. Section I.—Pisces. Subsection III.—Dipnoi. On the brain of the Ceratodus forsteri

1888 ◽  
Vol 43 (258-265) ◽  
pp. 420-423
Keyword(s):  
Fourth Ventricle ◽  
Third Ventricle ◽  
Pia Mater ◽  
The Third ◽  
Lateral Ventricles ◽  
Large Size ◽  
General Arrangement ◽  
Tela Choroidea ◽  
The Central Nervous System ◽  
The Brain

The brain of Ceratodus has the following general arrangement:—The membrane which represents the pia mater is of great thickness and toughness; there are two regions where a tela choroidea is developed: one where it covers in the fourth ventricle, and the other where it penetrates through the third ventricle and separates the lateral ventricles from each other. The ventricles are all of large size, and the walls of the lateral ventricles are not completed by nervous tissue. The thalamence-phalon and the mesencephalon are narrow, and the medulla oblongata is wide.

scholarly journals Pharmacologic Depletion of Microglia Increases Viral Load in the Brain and Enhances Mortality in Murine Models of Flavivirus-Induced Encephalitis

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Scott Seitz ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Immune Cells ◽  
Mrna Level ◽  
Cns Injury ◽  
Cytokines And Chemokines ◽  
Life Threatening ◽  
The Central Nervous System ◽  
The Brain ◽  
Stimulating Factor ◽  
Life Threatening Event

ABSTRACT Flaviviruses account for most arthropod-borne cases of human encephalitis in the world. However, the exact mechanisms of injury to the central nervous system (CNS) during flavivirus infections remain poorly understood. Microglia are the resident immune cells of the CNS and are important for multiple functions, including control of viral pathogenesis. Utilizing a pharmacologic method of microglia depletion (PLX5622 [Plexxikon Inc.], an inhibitor of colony-stimulating factor 1 receptor), we sought to determine the role of microglia in flaviviral pathogenesis. Depletion of microglia resulted in increased mortality and viral titer in the brain following infection with either West Nile virus (WNV) or Japanese encephalitis virus (JEV). Interestingly, microglial depletion did not prevent virus-induced increases in the expression of relevant cytokines and chemokines at the mRNA level. In fact, the expression of several proinflammatory genes was increased in virus-infected, microglia-depleted mice compared to virus-infected, untreated controls. In contrast, and as expected, expression of the macrophage marker triggering receptor expressed on myeloid cells 2 (TREM2) was decreased in virus-infected, PLX5622-treated mice compared to virus-infected controls. IMPORTANCE As CNS invasion by flaviviruses is a rare but life-threatening event, it is critical to understand how brain-resident immune cells elicit protection or injury during disease progression. Microglia have been shown to be important in viral clearance but may also contribute to CNS injury as part of the neuroinflammatory process. By utilizing a microglial depletion model, we can begin to parse out the exact roles of microglia during flaviviral pathogenesis with hopes of understanding specific mechanisms as potential targets for therapeutics.

scholarly journals Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System

2016 ◽  
Vol 90 (20) ◽  
pp. 9285-9292 ◽  
Author(s):  
Akiko Takenaka ◽  
Hiroki Sato ◽  
Fusako Ikeda ◽  
Misako Yoneda ◽  
Chieko Kai
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Hippocampal Formation ◽  
Target Cells ◽  
Canine Distemper ◽  
P Gene ◽  
The Central Nervous System ◽  
The Brain ◽  
Parental Mouse

ABSTRACTIn the current study, we generated recombinant chimeric canine distemper viruses (CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an avirulent strain expressing enhanced green fluorescent protein (EGFP) with those of a mouse-adapted neurovirulent strain. Anin vitroexperimental infection indicated that the chimeric CDVs possessing the H gene derived from the mouse-adapted CDV acquired infectivity for neural cells. These cells lack the CDV receptors that have been identified to date (SLAM and nectin-4), indicating that the H protein defines infectivity in various cell lines. The recombinant viruses were administered intracerebrally to 1-week-old mice. Fatal neurological signs of disease were observed only with a recombinant CDV that possessed both the H and P genes of the mouse-adapted strain, similar to the parental mouse-adapted strain, suggesting that both genes are important to drive virulence of CDV in mice. Using this recombinant CDV, we traced the intracerebral propagation of CDV by detecting EGFP. Widespread infection was observed in the cerebral hemispheres and brainstems of the infected mice. In addition, EGFP fluorescence in the brain slices demonstrated a sequential infectious progression in the central nervous system: CDV primarily infected the neuroependymal cells lining the ventricular wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and it then progressed to an extensive infection of the brain surface, followed by the parenchyma and cortex. In the hippocampal formation, CDV spread in a unidirectional retrograde pattern along neuronal processes in the hippocampal formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse model demonstrated that the main target cells of CDV are neurons in the acute phase and that the virus spreads via neuronal transmission pathways in the hippocampal formation.IMPORTANCECDV is the etiological agent of distemper in dogs and other carnivores, and in many respects, the pathogenesis of CDV infection in animals resembles that of measles virus infection in humans. We successfully generated a recombinant CDV containing the H and P genes from a mouse-adapted neurovirulent strain and expressing EGFP. The recombinant CDV exhibited severe neurovirulence with high mortality, comparable to the parental mouse-adapted strain. The mouse-infectious model could become a useful tool for analyzing CDV infection of the central nervous system subsequent to passing through the blood-cerebrospinal fluid barrier and infectious progression in the target cells in acute disease.

Brain Grafting as a Treatment for Parkinson's Disease

Neurosurgery ◽  
1987 ◽  
Vol 20 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Mark J. Perlow
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Manifestations ◽  
Dopamine Neurons ◽  
Clinical Aspects ◽  
Pathological Changes ◽  
Pharmacological Treatments ◽  
The Central Nervous System ◽  
The Brain

Abstract Parkinson's disease is an illness with neuropathological and neuroanatomical abnormalities in many areas of the central nervous system. Some clinical manifestations of this illness are correlated with pathological changes in the substantia nigra and with a loss of dopamine in the nigra and striatum. The most effective pharmacological treatments have used agents that either replace the lost dopamine or act as agonists on dopamine receptors. Recent studies in animal models of Parkinson's disease demonstrate that the loss of dopamine and many clinical manifestations of dopamine reduction can be reversed by transplantation of fetal dopamine-containing cells to specific dopamine-depleted areas of the brain. Long term viability of these transplants has also been demonstrated. The author suggests that the transplantation of dopamine neurons, even across species barriers, is a reasonable consideration for the treatment of human Parkinson's disease. This article reviews in detail the results of recent experiments and how the experience in these models might be utilized in determining a transplantation strategy for the treatment of specific clinical aspects of this illness.

scholarly journals Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

2021 ◽  
pp. 030098582110668
Author(s):  
Enric Vidal ◽  
Carlos López-Figueroa ◽  
Jordi Rodon ◽  
Mónica Pérez ◽  
Marco Brustolin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Neuronal Damage ◽  
Brain Lesions ◽  
Olfactory Mucosa ◽  
Histopathological Analysis ◽  
Post Inoculation ◽  
Vacuolar Degeneration ◽  
Early Entry ◽  
The Central Nervous System ◽  
The Brain

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.

scholarly journals Modern aspects of neuropathogenesis and neurological manifestations of COVID-19

2021 ◽  
Vol 17 (2) ◽  
pp. 6-15
Author(s):  
L.A. Dziak ◽  
O.S. Tsurkalenko ◽  
K.V. Chekha ◽  
V.M. Suk
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Symptoms ◽  
Clinical Manifestations ◽  
The Body ◽  
Altered Level ◽  
Wide Range ◽  
The Central Nervous System ◽  
The Brain

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.

scholarly journals SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

2020 ◽  
Author(s):  
Veronica Murta ◽  
Alejandro Villarreal ◽  
Alberto Javier Ramos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Experimental Models ◽  
Circumventricular Organs ◽  
Target Cells ◽  
Neurological Manifestations ◽  
Cns Inflammation ◽  
The Central Nervous System

With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.

scholarly journals Lymphocytic meningoencephalomyelitis associated with Myxobolus sp. (Bivalvulidae: Myxozoa) infection in the Amazonian fish Eigenmannia sp. (Sternopygidae: Gymnotiformes)

2016 ◽  
Vol 25 (2) ◽  
pp. 158-162 ◽  
Author(s):  
José Ledamir Sindeaux Neto ◽  
Michele Velasco ◽  
José Mauro Vianna da Silva ◽  
Patricia de Fátima Saco dos Santos ◽  
Osimar Sanches ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Histopathological Analysis ◽  
Administrative District ◽  
Amazon Estuary ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Hematoxylin Eosin

Abstract The genus Myxobolus, parasites that infect fishes, which cause myxobolosis, includes spore organisms belonging to the phylum Myxozoa and represents approximately 36% of all species described for the entire phylum. This study describes lymphocytic meningoencephalomyelitis associated with Myxobolus sp. infection in the brain and spinal cord (the central nervous system, CNS) of Eigenmannia sp., from the Amazon estuary region, in the Administrative District of Outeiro (DAOUT), Belém, Pará, Brazil. In May and June 2015, 40 Eigenmannia sp. specimens were captured from this region and examined. The fish were anesthetized, slaughtered and dissected for sexing (gonad evaluation) and studying parasites and cysts; after diagnosing the presence of the myxozoans using a light microscope, small fragments of the brain and spinal cord were removed for histological processing and Hematoxylin-Eosin and Ziehl-Neelsen staining. Histopathological analysis of the brain and spinal cord, based on histological sections stained with Hematoxylin-Eosin, pronounced and diffuse edema in these tissues, and congestion, degeneration, and focal necrosis of the cerebral cortex. The present study describes lymphocytic meningoencephalomyelitis associated with infection by Myxobolus sp. in the central nervous system of Eigenmannia sp.

scholarly journals Mortality Rate of CNS neoplasms in childhood in Brazil

2021 ◽  
Author(s):  
Nathália dos Santos Farias ◽  
Beatriz Silva Silveira ◽  
Isabela Mascarenhas de Andrade ◽  
Lara Cordeiro Magalhães ◽  
Maria Luísa Sousa Weber ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Clinical Manifestations ◽  
Secondary Data ◽  
Cns Tumors ◽  
Age Group ◽  
Incident Cancer ◽  
The Central Nervous System ◽  
Cns Neoplasms ◽  
Design And Methods ◽  
The Brain

Background: The variety of tumors of the Central Nervous System (CNS) during childhood is related to heterogenous clinical manifestations and to an important mortality rate (MR). In Brazil, CNS tumors represent the second most incident cancer during childhood and the main cause of death of children between ages 0-9. Objectives: To describe the number of hospitalizations and the MR of CNS neoplasms by childhood age group in Brazil. Design and Methods: This is a descriptive ecological study based on secondary data, obtained from DATASUS. Data were collected regarding the number of hospitalizations and MR by childhood age group due to neoplasm of the CNS in Brazil between the years 2009-2019. Results: A total of 38192 hospitalizations happened, resulting in 5.91% of MR. The highest value of brain’s neoplasms MR was found in children up to 1 year old (9,34%), but when it comes to number of hospitalizations, the group between ages 5-9 had the highest number, both in neoplasms of the brain (9364) and of other parts of the CNS (1767). Conclusions: The present study pointed out that the childhood age group with the lowest number of hospitalizations (less than 1 year) presented simultaneously the highest MR of CNS tumors.

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