scholarly journals Toxoplasma gondii Infections Alter GABAergic Synapses and Signaling in the Central Nervous System

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Justin M. Brooks ◽  
Gabriela L. Carrillo ◽  
Jianmin Su ◽  
David S. Lindsay ◽  
Michael A. Fox ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Toxoplasma Gondii ◽  
Acid Decarboxylase ◽  
Global Changes ◽  
Type Ii ◽  
Content Type ◽  
Gabaergic Synapses ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTDuring infections with the protozoan parasiteToxoplasma gondii, gamma-aminobutyric acid (GABA) is utilized as a carbon source for parasite metabolism and also to facilitate parasite dissemination by stimulating dendritic-cell motility. The best-recognized function for GABA, however, is its role in the nervous system as an inhibitory neurotransmitter that regulates the flow and timing of excitatory neurotransmission. When this pathway is altered, seizures develop. Human toxoplasmosis patients suffer from seizures, suggesting thatToxoplasmainterferes with GABA signaling in the brain. Here, we show that while excitatory glutamatergic presynaptic proteins appeared normal, infection with type II ME49Toxoplasmatissue cysts led to global changes in the distribution of glutamic acid decarboxylase 67 (GAD67), a key enzyme that catalyzes GABA synthesis in the brain. Alterations in GAD67 staining were not due to decreased expression but rather to a change from GAD67 clustering at presynaptic termini to a more diffuse localization throughout the neuropil. Consistent with a loss of GAD67 from the synaptic terminals,Toxoplasma-infected mice develop spontaneous seizures and are more susceptible to drugs that induce seizures by antagonizing GABA receptors. Interestingly, GABAergic protein mislocalization and the response to seizure-inducing drugs were observed in mice infected with type II ME49 but not type III CEP strain parasites, indicating a role for a polymorphic parasite factor(s) in regulating GABAergic synapses. Taken together, these data support a model in which seizures and other neurological complications seen inToxoplasma-infected individuals are due, at least in part, to changes in GABAergic signaling.IMPORTANCEInfections of the central nervous system can cause seizures. While inflammation in the brain has been proposed to initiate the onset of the seizures, relatively little is known about how inflammation impacts the structure and function of the neurons. Here we used a parasite calledToxoplasma gondiithat infects the brain and showed that seizures arise due to a defect in signaling of GABA, which is the neurotransmitter primarily responsible for preventing the onset of seizures.

Capillary hemangioma of the central nervous system

2004 ◽  
Vol 101 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Masamitsu Abe ◽  
Kazuo Tabuchi ◽  
Shin Tanaka ◽  
Akira Hodozuka ◽  
Katsuzo Kunishio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Capillary Hemangioma ◽  
Benign Tumors ◽  
Content Type ◽  
Perifocal Edema ◽  
The Central Nervous System ◽  
The Brain ◽  
Fine Print

Object. Capillary hemangiomas are benign tumors or tumorlike lesions that originate from blood vessels and have rarely been reported to develop in the brain or spinal cord. The authors summarize the clinical and histological features of capillary hemangiomas of the central nervous system (CNS). Methods. The clinical features, imaging characteristics, and outcomes in 10 patients with CNS capillary hemangiomas were reviewed. Histological studies included immunostaining with CD31, α-smooth muscle actin, vascular endothelial growth factor, and Ki-67 antigen. Three patients with lesions in the brain presented with symptoms of increased intracranial pressure or seizures. Seven patients with lesions in the spinal cord presented with progressive sensorimotor disturbances of the lower limbs. Computerized tomography and magnetic resonance imaging demonstrated well-defined, enhancing lesions associated with marked perifocal edema. Angiography demonstrated hypervascular lesions, which have not recurred after resection. In two cases, multiple satellite lesions resolved after the systemic administration of steroid drugs or interferon-α. Histologically, all lesions were consistent with findings of capillary hemangioma of the skin or soft tissues. The CNS lesions differed significantly from other vascular neoplasms, such as hemangioendotheliomas, hemangiopericytomas, and hemangioblastomas. Conclusions. Capillary hemangiomas of the CNS are benign lesions that can be surgically removed and cured without adjuvant therapy.

scholarly journals Blood-brain barrier-restricted translocation of Toxoplasma gondii from cortical capillaries

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gabriela C Olivera ◽  
Emily C Ross ◽  
Christiane Peuckert ◽  
Antonio Barragan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Toxoplasma Gondii ◽  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Cortical Capillaries ◽  
The Brain

The cellular barriers of the central nervous system proficiently protect the brain parenchyma from infectious insults. Yet, the single-celled parasite Toxoplasma gondii commonly causes latent cerebral infection in humans and other vertebrates. Here, we addressed the role of the cerebral vasculature in the passage of T. gondii to the brain parenchyma. Shortly after inoculation in mice, parasites mainly localized to cortical capillaries, in preference over post-capillary venules, cortical arterioles or meningeal and choroidal vessels. Early invasion to the parenchyma (days 1-5) occurred in absence of a measurable increase in blood-brain barrier (BBB) permeability, perivascular leukocyte cuffs or hemorrhage. However, sparse focalized permeability elevations were detected adjacently to replicative parasite foci. Further, T. gondii triggered inflammatory responses in cortical microvessels and endothelium. Pro- and anti-inflammatory treatments of mice with LPS and hydrocortisone, respectively, impacted BBB permeability and parasite loads in the brain parenchyma. Finally, pharmacological inhibition or Cre/loxP conditional knockout of endothelial focal adhesion kinase (FAK), a BBB intercellular junction regulator, facilitated parasite translocation to the brain parenchyma. The data reveal that the initial passage of T. gondii to the central nervous system occurs principally across cortical capillaries. The integrity of the microvascular BBB restricts parasite transit, which conversely is exacerbated by the inflammatory response.

Primary demyelinating disease simulating glioma of the corpus callosum

1981 ◽  
Vol 55 (4) ◽  
pp. 620-624 ◽  
Author(s):  
Kenneth G. Rieth ◽  
Giovanni Di Chiro ◽  
Laurence D. Cromwell ◽  
Paul E. McKeever ◽  
Paul L. Kornblith ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Corpus Callosum ◽  
Demyelinating Disease ◽  
Mass Effect ◽  
Periventricular White Matter ◽  
Content Type ◽  
The Central Nervous System ◽  
The Brain ◽  
Fine Print

✓ Computerized tomography (CT) has made it easier to distinguish tumoral from nontumoral diseases of the central nervous system. In the presence of mass effect, however, this distinction may be difficult or impossible to make. Primary demyelinating disease may occasionally present as a focal cerebral mass. The authors report three cases of primary demyelinating disease of the brain involving the corpus callosum and periventricular white matter and associated with mass effect, which proved difficult to differentiate from infiltrating “butterfly” gliomas.

Surface properties, more than size, limiting convective distribution of virus-sized particles and viruses in the central nervous system

2005 ◽  
Vol 103 (2) ◽  
pp. 311-319 ◽  
Author(s):  
Michael Y. Chen ◽  
Alan Hoffer ◽  
Paul F. Morrison ◽  
John F. Hamilton ◽  
Jeffrey Hughes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gray Matter ◽  
Extracellular Space ◽  
Invasive Technique ◽  
Major Barrier ◽  
Content Type ◽  
The Central Nervous System ◽  
The Brain ◽  
Fine Print

Object. Achieving distribution of gene-carrying vectors is a major barrier to the clinical application of gene therapy. Because of the blood—brain barrier, the distribution of genetic vectors to the central nervous system (CNS) is even more challenging than delivery to other tissues. Direct intraparenchymal microinfusion, a minimally invasive technique, uses bulk flow (convection) to distribute suspensions of macromolecules widely through the extracellular space (convection-enhanced delivery [CED]). Although acute injection into solid tissue is often used for delivery of oligonucleotides, viruses, and liposomes, and there is preliminary evidence that certain of these large particles can spread through the interstitial space of the brain by the use of convection, the use of CED for distribution of viruses in the brain has not been systematically examined. That is the goal of this study. Methods. Investigators used a rodent model to examine the influence of size, osmolarity of buffering solutions, and surface coating on the volumetric distribution of virus-sized nanoparticles and viruses (adeno-associated viruses and adenoviruses) in the gray matter of the brain. The results demonstrate that channels in the extracellular space of gray matter in the brain are large enough to accommodate virus-sized particles and that the surface characteristics are critical determinants for distribution of viruses in the brain by convection. Conclusions. These results indicate that convective distribution can be used to distribute therapeutic viral vectors in the CNS.

Nasal glioma and encephalocele: two separate entities

1986 ◽  
Vol 64 (3) ◽  
pp. 516-519 ◽  
Author(s):  
Mohammod Younus ◽  
Peter E. Coode
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Malignant Tumor ◽  
Malignant Potential ◽  
Developmental Abnormality ◽  
Content Type ◽  
Nasal Glioma ◽  
The Central Nervous System ◽  
The Brain ◽  
Fine Print

✓ The term “nasal glioma” is a confusing misnomer as it implies a neoplastic condition with malignant potential, which it is not. Nasal glioma is a rare developmental abnormality and should be differentiated from glioma, which is a malignant tumor of the brain, and from a primary encephalocele, which is herniation of the cranial contents through a bone defect in the skull, through which it retains an intact connection with the central nervous system. Two cases of nasal glioma, one with and one without intracranial connections, are described and the literature is reviewed.

scholarly journals Invasion of the Central Nervous System by Cryptococcus neoformans Requires a Secreted Fungal Metalloprotease

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Kiem Vu ◽  
Rick Tham ◽  
John P. Uhrig ◽  
George R. Thompson ◽  
Sarisa Na Pombejra ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Blood Brain Barrier ◽  
Brain Endothelium ◽  
Content Type ◽  
Extracellular Proteome ◽  
Cryptococcal Disease ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTCryptococcusspp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. WhyCryptococcus neoformanshas this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis ofC. neoformansrevealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome ofC. neoformans(CnMpr1) is required for establishing fungal disease in the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are expressed in only some fungal species. A strain ofC. neoformanslacking the gene encoding Mpr1 (mpr1Δ) failed to breach the endothelium in anin vitromodel of the human blood-brain barrier (BBB). A mammalian host infected with thempr1Δnull strain demonstrated significant improvement in survival due to a reduced brain fungal burden and lacked the brain pathology commonly associated with cryptococcal disease. Thein vivostudies further indicate that Mpr1 is not required for fungal dissemination and Mpr1 likely targets the brain endothelium specifically. Remarkably, the sole expression of CnMPR1inSaccharomyces cerevisiaeresulted in a robust migration of yeast cells across the brain endothelium, demonstrating Mpr1’s specific activity in breaching the BBB and suggesting that Mpr1 may function independently of the hyaluronic acid-CD44 pathway. This distinct role for Mpr1 may develop into innovative treatment options and facilitate a brain-specific drug delivery platform.IMPORTANCECryptococcus neoformansis a medically relevant fungal pathogen causing significant morbidity and mortality, particularly in immunocompromised individuals. An intriguing feature is its strong neurotropism, and consequently the hallmark of cryptococcal disease is a brain infection, cryptococcal meningoencephalitis. ForC. neoformansto penetrate the central nervous system (CNS), it first breaches the blood-brain barrier via a transcellular pathway; however, the identities of fungal factors required for this transmigration remain largely unknown. In an effort to identify extracellular fungal proteins that could mediate interactions with the brain endothelium, we undertook a proteomic analysis of the extracellular proteome and identified a secreted metalloprotease (Mpr1) belonging to the M36 class of fungalysins. Here we found that Mpr1 promotes migration ofC. neoformansacross the brain endothelium and into the CNS by facilitating attachment of cryptococci to the endothelium surface, thus underscoring the critical role of M36 proteases in fungal pathogenesis.

scholarly journals ARNOLD-CHIARI MALFORMATION: LITERATURE REVIEW AND CLINICAL CASE IN SIBLINGS

2021 ◽  
Vol 11 (1(39)) ◽  
pp. 58-64
Author(s):  
Anastasiya Babintseva ◽  
Yu.Yu. Khodzinska ◽  
І.V. Lastivka ◽  
О.І. Yurkiv ◽  
A.I. Roshka ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chiari Malformation ◽  
Clinical Case ◽  
Type Ii ◽  
Hernia Sac ◽  
Arnold Chiari Malformation ◽  
System Type ◽  
The Central Nervous System ◽  
The Brain

Arnold-Chiari malformation is a defectof the cervical-medullar transition characterized bydisplacement of the cerebellar tonsils and in a numberof cases when the stem and IV ventricle extend into theforamen magnum. There are four main types of pathology,and type II is found most often.The article presents a clinical case of type II ArnoldChiari malformation in siblings. The newborn girl born afterVII pregnancy and VII physiological delivery in the termof 39-40 weeks was under observation. US examination inthe terms of 20-21 and 34 weeks of gestation diagnoseda congenital developmental defect of the central nervoussystem characterized by a “lemon”-like shape of the brain,displacement of the brain structures in the portion of theforamen magnum, ventriculomegaly, a defect of the lumbarsacral portion with formation of hernia sac, and dropsy ofamnion. The family couple refused from interruption ofpregnancy and medical-genetic examination.The basic diagnosis of the child was congenitaldevelopmental defect of the central nervous system(type II Arnold-Chiari malformation: rachischisis andhydrocephalus) including complications such as inferiortorpid paraplegia and dysfunction of the pelvic organs.Investigation of hereditary anamnesis foundcompromised heredity on the mother’s side (her mother’ssibling has Down’s syndrome), and IV child in the familyis disabled from birth due to a congenital developmentaldefect of the central nervous system – type II Arnold-Chiarimalformation.The family couple refused from a comprehensivemedical-genetic consultation during the previous andcurrent pregnancies, and magnetic-resonance imaging ofthe child.

scholarly journals Cryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial Cells

2013 ◽  
Vol 81 (9) ◽  
pp. 3139-3147 ◽  
Author(s):  
Kiem Vu ◽  
Richard A. Eigenheer ◽  
Brett S. Phinney ◽  
Angie Gelli
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Human Brain ◽  
Cryptococcus Neoformans ◽  
Brain Endothelial Cells ◽  
Brain Endothelium ◽  
Content Type ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTCryptococcusspp. cause fungal meningitis, a life-threatening infection that occurs predominately in immunocompromised individuals. In order forCryptococcus neoformansto invade the central nervous system (CNS), it must first penetrate the brain endothelium, also known as the blood-brain barrier (BBB). Despite the importance of the interrelation betweenC. neoformansand the brain endothelium in establishing CNS infection, very little is known about this microenvironment. Here we sought to resolve the cellular and molecular basis that defines the fungal-BBB interface during cryptococcal attachment to, and internalization by, the human brain endothelium. In order to accomplish this by a systems-wide approach, the proteomic profile of human brain endothelial cells challenged withC. neoformanswas resolved using a label-free differential quantitative mass spectrometry method known as spectral counting (SC). Here, we demonstrate that as brain endothelial cells associate with, and internalize, cryptococci, they upregulate the expression of several proteins involved with cytoskeleton, metabolism, signaling, and inflammation, suggesting that they are actively signaling and undergoing cytoskeleton remodeling via annexin A2, S100A10, transgelin, and myosin. Transmission electronic microscopy (TEM) analysis demonstrates dramatic structural changes in nuclei, mitochondria, the endoplasmic reticulum (ER), and the plasma membrane that are indicative of cell stress and cell damage. The translocation of HMGB1, a marker of cell injury, the downregulation of proteins that function in transcription, energy production, protein processing, and the upregulation of cyclophilin A further support the notion thatC. neoformanselicits changes in brain endothelial cells that facilitate the migration of cryptococci across the BBB and ultimately induce endothelial cell necrosis.

scholarly journals STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Shinya Hidano ◽  
Louise M. Randall ◽  
Lucas Dawson ◽  
Hans K. Dietrich ◽  
Christoph Konradt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Toxoplasma Gondii ◽  
Critical Role ◽  
Opportunistic Pathogen ◽  
Protective Effects ◽  
The Central Nervous System ◽  
Parasite Replication ◽  
Ifn Γ ◽  
The Brain

ABSTRACTThe local production of gamma interferon (IFN-γ) is important to controlToxoplasma gondiiin the brain, but the basis for these protective effects is not fully understood. The studies presented here reveal that the ability of IFN-γ to inhibit parasite replication in astrocytesin vitrois dependent on signal transducer and activator of transcription 1 (STAT1) and that mice that specifically lack STAT1 in astrocytes are unable to limit parasite replication in the central nervous system (CNS). This susceptibility is associated with a loss of antimicrobial pathways and increased cyst formation in astrocytes. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen.IMPORTANCEAstrocytes are the most numerous cell type in the brain, and they are activated in response to many types of neuroinflammation, but their function in the control of CNS-specific infection is unclear. The parasiteToxoplasma gondiiis one of the few clinically relevant microorganisms that naturally infects astrocytes, and the studies presented here establish that the ability of astrocytes to inhibit parasite replication is essential for the local control of this opportunistic pathogen. Together, these studies establish a key role for astrocytes as effector cells and in the coordination of many aspects of the protective immune response that operates in the brain.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

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