Early detection of liposome brain localization in rat experimental allergic encephalomyelitis

Blood-brain barrier (BBB) permeability increases prior to the development o f clinical signs in early-stage multiple sclerosis;(MS). Detection of subtl e changes would thus be helpful for diagnostic purposes and rapid therapeut ic decisions before new episodes. Since multiple sclerosis and experimental allergic encephalomyelitis (EAE) have numerous common features, in particu lar BBB-permeability characteristics, and since we have previously shown th at BBB localization is disturbed by tumors, embolism, and mannitol injectio n, we investigated BBB-liposome permeability in an EAE rat model. Twenty yo ung male Lewis rats received a single intradermal inoculation of guinea-pig spinal cord. The effect of the Freund's adjuvant and spinal cord alone on brain permeability were also assessed. In order to compare solution permeab ility and liposome localization, radioactive liposomes and, 1 h later, Tc-9 9m-DTPA were injected intravenously. Scintigraphic acquisitions were obtain ed to follow the biodistribution of radioactivity in the whole body. Each r at was subjected to a first examination before inoculation and then every t wo days until completion and may be considered as its own control. EAE indu ced a previously unreported increase in global-body permeability, probably due to inflammation. Liposome brain localization and brain/heart ratio were significantly different between normal animals and those with early-stage EAE (before appearance of clinical signs) and distinguished between differe nt disease stages in clinically patent EAE. The index of disease progressio n was modified earlier than with 99mTc-DTPA injection. One explanation may be particle pick-up by circulating macrophages, which cross the BBB during this pathology. For clinical applications, experiments must be confirmed on models more reliable for human multiple sclerosis.