Dysfunctional Glymphatic System with Disrupted Aquaporin 4 Expression Pattern on Astrocytes Causes Bacterial Product Accumulation in the CSF during Pneumococcal Meningitis

Generoso, Jaqueline S.; Thorsdottir, Sigrun; Collodel, Allan; Dominguini, Diogo; Santo, Roberta R. E.; Petronilho, Fabrícia; Barichello, Tatiana; Iovino, Federico

doi:10.1128/mbio.01886-22

Cited by 14 publications

(9 citation statements)

References 68 publications

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“…Pneumolysin (Ply) is the pore-forming cytotoxin released by S. pneumoniae and can damage the host cells ( 56 , 57 ). Generoso et al, have recently shown that the accumulation of pneumococci and toxic pneumococcal products, such as Ply, in the CSF compartments of the brain leads to neuronal damage with consequent dramatic impairment of neurological functions ( 58 ). Like it was previously described for other bacterial pathogens, pneumococci can exploit the interaction with the host cell cytoskeleton to invade neurons; neuronal cell death occurs due to cytoskeleton disruption ( 59 , 60 ).…”

Section: Neuroinflammation and Role Of Microglia In Bacterial Meningitismentioning

confidence: 99%

Bacterial meningitis in Africa

Barichello

Catalão²,

Rohlwink³

et al. 2023

Front. Neurol.

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Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group B Streptococcus), Escherichia coli, and Staphylococcus aureus are neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics.

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Section: Neuroinflammation and Role Of Microglia In Bacterial Meningitismentioning

confidence: 99%

Bacterial meningitis in Africa

Barichello

Catalão²,

Rohlwink³

et al. 2023

Front. Neurol.

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“…To determine if astrocytes, a key component in the VZ disruption due to the reactive astrogliosis associated with hydrocephalus pathology [ 43 ] and as a structural component of the glymphatic system involved in the parenchymal CSF pathway [ 38 , 44 ], were affected by increased concentrations of DMSO, transwell astrocyte cultures were performed. Astrocyte viability was evaluated in cell cultures ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Intraventricular dimethyl sulfoxide (DMSO) induces hydrocephalus in a dose-dependent pattern

Castaneyra-Ruiz,

Ledbetter,

Lee

et al. 2024

Heliyon

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“…Perhaps, the protective effect of antimicrobial therapeutics is due to the mitigation of the contribution of infections to the progression of AD pathology. Indeed, experimental studies have revealed significant impairment of the glymphatic system following cerebral infection (e.g., pneumococcal meningitis) [ 151 ], which could exacerbate AD progression at all stages of disease. Moreover, the prolonged activation of immune cells is a central feature of AD and induces a pro-inflammatory cascade that contributes to neuronal loss.…”

Section: Discussionmentioning

confidence: 99%

Clinical evidence of human pathogens implicated in Alzheimer’s disease pathology and the therapeutic efficacy of antimicrobials: an overview

Catumbela

Giridharan

Barichello

et al. 2023

Transl Neurodegener

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A wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer’s disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet clear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain. Along the same line, the gut microbiome has also been proposed as a modulator of AD. In this review, we focus on human-based evidence demonstrating the elevated abundance of microbes and microbe-derived molecules in AD hosts as well as their interactions with AD hallmarks. Further, the direct-purpose and potential off-target effects underpinning the efficacy of anti-microbial treatments in AD are also addressed.

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Dysfunctional Glymphatic System with Disrupted Aquaporin 4 Expression Pattern on Astrocytes Causes Bacterial Product Accumulation in the CSF during Pneumococcal Meningitis

Cited by 14 publications

References 68 publications

Bacterial meningitis in Africa

Bacterial meningitis in Africa

Intraventricular dimethyl sulfoxide (DMSO) induces hydrocephalus in a dose-dependent pattern

Clinical evidence of human pathogens implicated in Alzheimer’s disease pathology and the therapeutic efficacy of antimicrobials: an overview

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