scholarly journals Streptococcus pneumoniae rapidly translocates from the nasopharynx through the cribriform plate to invade and inflame the dura

2021 ◽  
Author(s):  
Teerawit Audshasai ◽  
Jonathan A. Coles ◽  
Stavros Panagiotou ◽  
Shadia Khandaker ◽  
Hannah E. Scales ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Streptococcus Pneumoniae ◽  
Bacterial Pathogens ◽  
Horizontal Transmission ◽  
Cribriform Plate ◽  
Dorsal Cortex ◽  
Invasion Mechanisms ◽  
Viable Bacteria ◽  
The Central Nervous System

AbstractThe entry routes and translocation mechanisms of bacterial pathogens into the central nervous system remain obscure. We report here that Streptococcus pneumoniae (Sp) or polystyrene microspheres, applied to the nose of a mouse, appeared in the meninges of the dorsal cortex within minutes. Recovery of viable bacteria from dissected tissue and fluorescence microscopy showed that up to at least 72h, Sp and microspheres were predominantly in the outer of the two meninges, the pachymeninx. No Sp were found in blood or cerebrospinal fluid. Evidence that this was not an artifact of the method of administration is that in mice infected by horizontal transmission, Sp were also predominantly in the meninges and absent from blood. Intravital imaging through the skull, and flow cytometry showed recruitment and activation of LysM+ cells in the dorsal pachymeninx at 5h and 10h following intranasal infection. Imaging of the cribriform plate suggested that both Sp and microspheres entered through its foramina via an inward flow of fluid connecting the nose to the pachymeninx. Our findings bring further insight into the invasion mechanisms of bacterial pathogens such as Sp into the central nervous system, but are also pertinent to the delivery of drugs to the brain, and the entry of air-borne particles into the cranium.

scholarly journals The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System

2018 ◽  
Vol 27 (3) ◽  
pp. 501-514 ◽  
Author(s):  
Carlos Galeano ◽  
Zhifang Qiu ◽  
Anuja Mishra ◽  
Steven L. Farnsworth ◽  
Jacob J. Hemmi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Nasal Cavity ◽  
Olfactory Epithelium ◽  
Cribriform Plate ◽  
Intranasal Delivery ◽  
Immunodeficient Mice ◽  
Stem Cell Delivery ◽  
The Central Nervous System

Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton’s jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.

scholarly journals High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins.

1996 ◽  
Vol 40 (1) ◽  
pp. 218-220 ◽  
Author(s):  
P F Viladrich ◽  
C Cabellos ◽  
R Pallares ◽  
F Tubau ◽  
J Martínez-Lacasa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Streptococcus Pneumoniae ◽  
Broad Spectrum ◽  
Adjunctive Therapy ◽  
Maximum Dose ◽  
Central Nervous System Infection ◽  
The Central Nervous System ◽  
High Doses

We treated nine patients (10 episodes) with meningitis caused by Streptococcus pneumoniae isolates with decreased susceptibilities to broad-spectrum cephalosporins with high doses of cefotaxime (300 mg/kg of body weight per day; maximum dose, 24 g/day). Early adjunctive therapy with dexamethasone was also administered. Cefotaxime MICs were 0.5 (three episodes), 1 (five episodes), and 2 (two episodes) micrograms/ml, and MBCs ranged from 1 to 4 micrograms/ml. Therapy was well tolerated, and all patients experienced prompt clinical improvement. One patient died 8 days after the end of therapy, the central nervous system infection had already been cured, and the remaining patients recovered without relapses.

scholarly journals Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System

2016 ◽  
Vol 84 (9) ◽  
pp. 2607-2615 ◽  
Author(s):  
Brandon L. Hatcher ◽  
Joanetha Y. Hale ◽  
David E. Briles
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Streptococcus Pneumoniae ◽  
Sialic Acid ◽  
Bacterial Meningitis ◽  
Imaging System ◽  
Pneumococcal Infection ◽  
Acute Bacterial Meningitis ◽  
Olfactory Bulbs ◽  
The Central Nervous System

Streptococcus pneumoniae(pneumococcus) is a leading cause of bacterial meningitis and neurological sequelae in children worldwide. Acute bacterial meningitis is widely considered to result from bacteremia that leads to blood-brain barrier breakdown and bacterial dissemination throughout the central nervous system (CNS). Previously, we showed that pneumococci can gain access to the CNS through a nonhematogenous route without peripheral blood infection. This access is thought to occur when the pneumococci in the upper sinus follow the olfactory nerves and enter the CNS through the olfactory bulbs. In this study, we determined whether the addition of exogenous sialic acid postcolonization promotes nonhematogenous invasion of the CNS. Previously, others showed that treatment with exogenous sialic acid post-pneumococcal infection increased the numbers of CFU recovered from an intranasal mouse model of infection. Using a pneumococcal colonization model, anin vivoimaging system, and a multiplex assay for cytokine expression, we demonstrated that sialic acid can increase the number of pneumococci recovered from the olfactory bulbs and brains of infected animals. We also show that pneumococci primarily localize to the olfactory bulb, leading to increased expression levels of proinflammatory cytokines and chemokines. These findings provide evidence that sialic acid can enhance the ability of pneumococci to disseminate into the CNS and provide details about the environment needed to establish nonhematogenous pneumococcal meningitis.

scholarly journals Streptococcus pneumoniae Causes Experimental Meningitis following Intranasal and Otitis Media Infections via a Nonhematogenous Route

2001 ◽  
Vol 69 (12) ◽  
pp. 7318-7325 ◽  
Author(s):  
Andrea Marra ◽  
Daniel Brigham
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Intranasal Inoculation ◽  
The Central Nervous System ◽  
Human Infections ◽  
The Brain ◽  
Do So

ABSTRACT Using two different animal models of Streptococcus pneumoniae infection, we have demonstrated that this organism is able to spread to the central nervous system and cause meningitis by bypassing the bloodstream. Following respiratory tract infection induced via intranasal inoculation, bacteria were rapidly found in the bloodstream and brains in the majority of infected mice. A similar pattern of dissemination occurred following otitis media infection via transbullar injection of gerbils. However, a small percentage of animals infected by either route showed no bacteria in the blood and yet did have significant numbers of bacteria in brain tissue. Subsequent experiments using a galU mutant of S. pneumoniae, which is impaired in its ability to disseminate to the bloodstream following infection, showed that this organism is able to spread to the brain and cerebrospinal fluid. These results demonstrate that, unlike many bacterial pathogens that cause meningitis, S. pneumoniae is able to do so independent of bloodstream involvement upon different routes of infection. This may address the difficulty in treating human infections caused by this organism.

scholarly journals Invasion of the Central Nervous System by Intracellular Bacteria

2004 ◽  
Vol 17 (2) ◽  
pp. 323-347 ◽  
Author(s):  
Douglas A. Drevets ◽  
Pieter J. M. Leenen ◽  
Ronald A. Greenfield
Keyword(s):  
Experimental Data ◽  
Central Nervous System ◽  
Nervous System ◽  
Bacterial Pathogens ◽  
Life Cycles ◽  
Cns Infection ◽  
Recent Experimental Data ◽  
Intracellular Bacteria ◽  
Obligate Intracellular ◽  
The Central Nervous System

SUMMARY Infection of the central nervous system (CNS) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. Examples of these include the facultative intracellular bacteria Listeria monocytogenes, Mycobacterium tuberculosis, and Brucella and Salmonella spp. and obligate intracellular microbes of the Rickettsiaceae family and Tropheryma whipplei. Unfortunately, the mechanisms used by intracellular bacterial pathogens to enter the CNS are less well known than those used by bacterial pathogens with an extracellular life cycle. The goal of this review is to elaborate on the means by which intracellular bacterial pathogens establish infection within the CNS. This review encompasses the clinical and pathological findings that pertain to the CNS infection in humans and includes experimental data from animal models that illuminate how these microbes enter the CNS. Recent experimental data showing that L. monocytogenes can invade the CNS by more than one mechanism make it a useful model for discussing the various routes for neuroinvasion used by intracellular bacterial pathogens.

Effects of Hyperoxia on Lung Utrastructure

1970 ◽  
Vol 28 ◽  
pp. 26-27
Author(s):  
Gladys Harrison
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Light Microscopy ◽  
Oxygen Effects ◽  
Age Dependent ◽  
The Central Nervous System ◽  
The Subject ◽  
Space Age ◽  
Alveolar Septa ◽  
Extensive Damage

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.

Emigration of neutrophils in the central nervous system

1983 ◽  
Vol 41 ◽  
pp. 788-789
Author(s):  
John L.Beggs ◽  
John D. Waggener ◽  
Wanda Miller ◽  
Jane Watkins
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Osmium Tetroxide ◽  
White Blood Cells ◽  
Arterial Perfusion ◽  
E Coli ◽  
Intracisternal Injection ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
Interendothelial Junctions

Studies using mesenteric and ear chamber preparations have shown that interendothelial junctions provide the route for neutrophil emigration during inflammation. The term emigration refers to the passage of white blood cells across the endothelium from the vascular lumen. Although the precise pathway of transendo- thelial emigration in the central nervous system (CNS) has not been resolved, the presence of different physiological and morphological (tight junctions) properties of CNS endothelium may dictate alternate emigration pathways.To study neutrophil emigration in the CNS, we induced meningitis in guinea pigs by intracisternal injection of E. coli bacteria.In this model, leptomeningeal inflammation is well developed by 3 hr. After 3 1/2 hr, animals were sacrificed by arterial perfusion with 3% phosphate buffered glutaraldehyde. Tissues from brain and spinal cord were post-fixed in 1% osmium tetroxide, dehydrated in alcohols and propylene oxide, and embedded in Epon. Thin serial sections were cut with diamond knives and examined in a Philips 300 electron microscope.

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