Tryps and trips: cell trafficking across the 100-year-old blood-brain barrier

Trends Neurosci. 2014 Jun;37(6):325-33. doi: 10.1016/j.tins.2014.03.007. Epub 2014 Apr 27.

Abstract

One hundred years ago, Edwin E. Goldmann discovered the blood-brain barrier (BBB) using trypan dyes. These dyes were developed and named by Paul Ehrlich during his search for drugs to kill African trypanosomes (extracellular parasites that cause sleeping sickness) while sparing host cells. For Ehrlich, this was the first strategy based on the 'chemotherapy' concept he had introduced. The discovery of the BBB revealed, however, the difficulties in drug delivery to the brain. Mechanisms by which parasites enter, dwell, and exit the brain currently provide novel views on cell trafficking across the BBB. These mechanisms also highlight the role of pericytes and endocytosis regulation in BBB functioning and in disrupted BBB gating, which may be involved in the pathogenesis of neurodegeneration.

Keywords: endocytosis; neurodegeneration; neuroinflammation; neurovascular unit; pericytes; sleeping sickness.

Publication types

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

MeSH terms

  • Animals
  • Azo Compounds / pharmacology*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / parasitology
  • Blood-Brain Barrier / physiology*
  • Blood-Brain Barrier / physiopathology
  • Brain / drug effects
  • Brain / parasitology
  • Brain / physiology
  • Brain / physiopathology
  • Cell Movement / physiology*
  • Coloring Agents / pharmacology*
  • History, 19th Century
  • History, 20th Century
  • Humans
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / physiopathology
  • Neurology / history
  • Trypanocidal Agents / pharmacology*
  • Trypanosomiasis / drug therapy
  • Trypanosomiasis / physiopathology

Substances

  • Azo Compounds
  • Coloring Agents
  • Trypanocidal Agents