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

Neuropathol Appl Neurobiol. 2009 Apr;35(2):132-46. doi: 10.1111/j.1365-2990.2008.01005.x. Epub 2008 Dec 11.

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 neurodegenerative 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / immunology
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Animals
  • Blood-Brain Barrier / physiopathology*
  • Brain / growth & development*
  • Brain / immunology
  • Brain / pathology
  • Cerebral Palsy / immunology
  • Cerebral Palsy / pathology
  • Cerebral Palsy / physiopathology
  • Humans
  • Inflammation / physiopathology*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Neurodegenerative Diseases / immunology
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology*
  • Parkinson Disease / immunology
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Schizophrenia / immunology
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology