Spatial diversity of blood-brain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: a comparative MRI study

Exp Neurol. 2009 Nov;220(1):207-11. doi: 10.1016/j.expneurol.2009.08.027. Epub 2009 Sep 4.


Inflammation plays a central role in the development of numerous disorders of the central nervous system (CNS) such as multiple sclerosis (MS). For a long time it was assumed that recruitment of macrophages into the CNS and breakdown of the blood-brain barrier (BBB) are closely linked. In the present study we challenge this concept. We used small superparamagnetic iron oxide particles (SPIO)-enhanced T2-weighted (T2-w) magnetic resonance imaging (MRI) on a routine 1.5 T MRI unit to follow macrophage infiltration in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. After an initial SPIO-enhanced MRI, gadofluorine M (Gf), an experimental contrast agent which proved to be more sensitive in detecting BBB leakage than gadolinium (Gd)-DTPA (Bendszus, M., Ladewig, G., Jestaedt, L., Misselwitz, B., Solymosi, L., Toyka, K.V., Stoll, G., Gadofluorine-M enhancement allows more sensitive detection of inflammatory CNS lesions than T2-w imaging: a quantitative MRI study. Brain 2008; 1-12), was applied to the same animals followed by a second scan. Areas with SPIO-induced signal loss on T2-w MRI indicative of recent macrophage infiltration were matched with areas showing Gf enhancement as a measure of BBB disturbance. Overall 87 EAE lesions showed iron-related signal loss, while 57 lesions showed Gf enhancement. By direct comparison we could detect concomitant SPIO-induced signal loss and Gf enhancement only in a small minority of lesions. In conclusion, our findings show macrophage infiltration in the CNS during EAE in areas with a closed BBB for humoral factors. This holds true despite the use of a more sensitive MR contrast agent for BBB disruption than Gd-DTPA. Our experimental observations may have implications for disease monitoring in MS patients by MRI which guides treatment decisions.

Publication types

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

MeSH terms

  • Animals
  • Blood-Brain Barrier / pathology*
  • Blood-Brain Barrier / physiopathology*
  • Chemotaxis, Leukocyte / physiology*
  • Contrast Media
  • Disease Models, Animal
  • Disease Progression
  • Encephalitis / pathology
  • Encephalitis / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Female
  • Ferric Compounds
  • Macrophages / cytology
  • Macrophages / physiology*
  • Magnetic Resonance Imaging / methods
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Organometallic Compounds
  • Predictive Value of Tests
  • Rats
  • Sensitivity and Specificity


  • Contrast Media
  • Ferric Compounds
  • Organometallic Compounds
  • gadofluorine
  • ferric oxide