The "window of susceptibility" for inflammation in the immature central nervous system is characterized by a leaky blood-brain barrier and the local expression of inflammatory chemokines

Neurobiol Dis. 2009 Sep;35(3):368-75. doi: 10.1016/j.nbd.2009.05.026. Epub 2009 Jun 9.

Abstract

Early in postnatal development, the immature central nervous system (CNS) is more susceptible to inflammation than its adult counterpart. We show here that this "window of susceptibility" is characterized by the presence of leaky vessels in the CNS, and by a global chemokine expression profile which is clearly distinct from the one observed in the adult CNS and has three important characteristics. First, it contains chemokines with known roles in the differentiation and maturation of glia and neurons. Secondly, these chemokines have been described before in inflammatory lesions of the CNS, where they are important for the recruitment of monocytes and T cells. Lastly, the chemokine profile is shaped by pathological changes like oligodendrocyte stress and attempts of myelin repair. Changes in the chemokine expression profile along with a leaky blood-brain barrier pave the ground for an accelerated development of CNS inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Animals, Newborn
  • Blood-Brain Barrier / growth & development*
  • Blood-Brain Barrier / immunology*
  • Blood-Brain Barrier / metabolism
  • CD3 Complex / metabolism
  • CD8 Antigens / metabolism
  • Capillary Permeability / physiology
  • Chemokines / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Granulocytes / physiology
  • Macrophages / physiology
  • Myelin Proteolipid Protein / genetics
  • Neuroimmunomodulation / physiology
  • Rats
  • Rats, Inbred Lew
  • Rats, Transgenic
  • Spinal Cord / blood supply
  • Spinal Cord / growth & development*
  • Spinal Cord / immunology*
  • T-Lymphocytes / physiology

Substances

  • CD3 Complex
  • CD8 Antigens
  • Chemokines
  • Myelin Proteolipid Protein
  • Plp1 protein, rat