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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.
Generoso, Jaqueline S; Thorsdottir, Sigrun; Collodel, Allan; Dominguini, Diogo; Santo, Roberta R E; Petronilho, Fabricia; Barichello, Tatiana; Iovino, Federico.
Afiliação
  • Generoso JS; Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.
  • Thorsdottir S; Department of Neuroscience, Karolinska Institutegrid.4714.6t, Biomedicum, Stockholm, Sweden.
  • Collodel A; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.
  • Dominguini D; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.
  • Santo RRE; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.
  • Petronilho F; Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.
  • Barichello T; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.
  • Iovino F; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houstongrid.267308.8, Houston, Texas, USA.
mBio ; 13(5): e0188622, 2022 10 26.
Article em En | MEDLINE | ID: mdl-36036510
Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of the glymphatic system by retaining the EBA in the CSF compartments compared to the uninfected sham group. Our results clearly showed that during pneumococcal meningitis, the glymphatic system does not function because of a detachment of the astrocytic end feet from the blood-brain barrier (BBB) vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel's functionality. IMPORTANCE The lack of solute drainage due to a dysfunctional glymphatic system leads to an increase of the neurotoxic bacterial material in the CSF compartments of the brain, ultimately leading to brain-wide neuroinflammation and neuronal damage with consequent impairment of neurological functions. The loss of function of the glymphatic system can therefore be a leading cause of the neurological sequelae developing post-bacterial meningitis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistema Glinfático / Meningite Pneumocócica Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: MBio Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistema Glinfático / Meningite Pneumocócica Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: MBio Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos