Disruption of the Blood-Brain Barrier During Neuroinflammatory and Neuroinfectious Diseases

  • Hamid Salimi
  • Robyn S. KleinEmail author
Part of the Contemporary Clinical Neuroscience book series (CCNE)


As the organ of highest metabolic demand, utilizing over 25% of total body glucose utilization via an enormous vasculature with one capillary every 73 μm, the brain evolves a barrier at the capillary and postcapillary venules to prevent toxicity during serum fluctuations in metabolites and hormones, to limit brain swelling during inflammation, and to prevent pathogen invasion. Understanding of neuroprotective barriers has since evolved to incorporate the neurovascular unit (NVU), the blood-cerebrospinal fluid (CSF) barrier, and the presence of CNS lymphatics that allow leukocyte egress. Identification of the cellular and molecular participants in BBB function at the NVU has allowed detailed analyses of mechanisms that contribute to BBB dysfunction in various disease states, which include both autoimmune and infectious etiologies. This chapter will introduce some of the cellular and molecular components that promote barrier function but may be manipulated by inflammatory mediators or pathogens during neuroinflammation or neuroinfectious diseases.


Blood-brain barrier Neuroinfectious diseases Tight junctions Innate immunity Central nervous system 



Adherens junction




Antigen-presenting cell


Aquaporin 4


Blood-brain barrier


Basic fibroblast growth factor


Brain microvascular endothelial cell




Cerebral blood flow


Chikungunya virus


Central nervous system


Cerebrospinal fluid


Chondroitin sulfate proteoglycan


Cytotoxic T cell


Prostaglandin D2 receptor 1


Double-stranded ribonucleic acid


Endothelial cell


Experimental cerebral malaria


Extracellular matrix


Extracellular signal-regulated protein kinase


Edema toxin


Gadolinium MRI


Glial cell line-derived neurotrophic factor


Hendra virus


Human immunodeficiency virus type 1


Herpes simplex virus


Intercellular adhesion molecule 1




Type I IFN receptor




Infected RBC


Japanese encephalitis virus


Lymphocytic choriomeningitis virus


Mitogen-activated protein kinase


Mouse adenovirus type-1


Mitochondrial antiviral-signaling protein


Melanoma differentiation factor 5


Tyrosine-protein kinase Mer


Major facilitator superfamily domain-containing protein 2a


Mouse hepatitis virus


Matrix metalloproteinase


Magnetic resonance imaging


Multiple sclerosis


Meningococcal serine protease


Nicotinamide adenine dinucleotide phosphate


Nipah virus


Nucleotide oligomerization domain-like receptor


Neuromyelitis optica spectrum disorder


Neurovascular unit




Platelet-activating factor receptor


Platelet-derived growth factor BB


Platelet-derived growth factor receptor β


Platelet-associated cell adhesion molecule 1




Prostaglandin D2


Phosphatidylinositol 3 kinase


Polymeric immunoglobulin receptor


Protein kinase B


Phospholipase C


Primary progressive multiple sclerosis


Pattern recognition receptor


Rabies virus


Ras-related C3 botulinum toxin substrate


Red blood cell


Ras homolog gene family, member A


Retinoic acid-inducible gene 1 like receptor


Reactive oxygen species


Recovery and remission multiple sclerosis




Subarachnoid space


Soluble CD40L


Sonic hedgehog


Secondary-progressive multiple sclerosis


Single-stranded ribonucleic acid


Tick-borne encephalitic virus


Transendothelial electrical resistance


Endogenous tissue inhibitor of MMP


Tight junction


Toll-like receptor


Theiler’s murine encephalitis virus


Tumor necrosis factor alpha


Vascular cell adhesion molecule 1


Venezuelan equine encephalitis virus


Vascular endothelial growth factor


Vesicular stomatitis virus


West Nile virus


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Departments of MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Departments of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA
  3. 3.Departments of NeuroscienceWashington University School of MedicineSt. LouisUSA
  4. 4.Division of Biology and Biomedical SciencesCenter for Neuroimmunology & Neuroinfectious Diseases, Washington University School of MedicineSt. LouisUSA

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