Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases

H. B. Stolp*, K. M. Dziegielewska

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

210 Citations (Scopus)

Abstract

The causes of most neurological disorders are not fully understood. Inflammation and blood-brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders. In this review, a new hypothesis suggesting a mechanistic link between inflammation and blood-brain barrier function (integrity), which is universally important in both neurodevelopmental and neurodegerative diseases, is proposed. The role of inflammation and the blood-brain barrier will be discussed in cerebral palsy, schizophrenia, Parkinson's disease, Alzheimer's disease and multiple sclerosis, conditions where both inflammation and blood-brain barrier dysfunction occur either during initiation and/or progression of the disease. We suggest that breakdown of normal blood-brain barrier function resulting in a short-lasting influx of blood-born molecules, in particular plasma proteins, may cause local damage, such as reduction of brain white matter observed in some newborn babies, but may also be the mechanism behind some neurodegenerative diseases related to underlying brain damage and long-term changes in barrier properties.

Original languageEnglish
Pages (from-to)132-146
Number of pages15
JournalNeuropathology and Applied Neurobiology
Volume35
Issue number2
DOIs
Publication statusPublished - Apr 2009

Keywords

  • blood-brain barrier
  • brain development
  • inflammation
  • neurodegeneration
  • EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • LATE OLIGODENDROCYTE PROGENITORS
  • MICROVESSEL ENDOTHELIAL-CELLS
  • OPOSSUM MONODELPHIS-DOMESTICA
  • BACTERIAL-ENDOTOXIN EXPOSURE
  • TIGHT JUNCTION PROTEINS
  • APPEARING WHITE-MATTER
  • CENTRAL-NERVOUS-SYSTEM
  • MULTIPLE-SCLEROSIS

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