Early detection of liposome brain localization in rat experimental allergic encephalomyelitis

• Published in: Experimental brain research Vol. 125; no. 3; pp. 255 - 264
• Main Authors: ROUSSEAU, V, DENIZOT, B, LE JEUNE, J. J, JALLET, P
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.04.1999
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Freund's Adjuvant - pharmacology; Guinea Pigs; Kidney - metabolism; Liposomes - pharmacokinetics; Liver - metabolism; Male; Medical sciences; Multiple Sclerosis - metabolism; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myocardium - metabolism; Nerve Tissue Proteins - pharmacokinetics; Neurology; Rats; Rats, Inbred Lew; Spinal Cord - chemistry; Spinal Cord - metabolism; Spleen - metabolism; Technetium Tc 99m Pentetate - pharmacokinetics; Tissue Distribution; Urinary Bladder - metabolism; Immunopathology; Nervous system diseases; Multiple sclerosis; Encephalomyelitis; Rat; Pathogenesis; Rodentia; Liposome; Autoimmune disease; Permeability; Blood brain barrier; Inflammatory disease; Vertebrata; Mammalia; Animal; Central nervous system disease; Brain (vertebrata)
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s002210050681

Blood-brain barrier (BBB) permeability increases prior to the development of clinical signs in early-stage multiple sclerosis (MS). Detection of subtle changes would thus be helpful for diagnostic purposes and rapid therapeutic decisions before new episodes. Since multiple sclerosis and experimental allergic encephalomyelitis (EAE) have numerous common features, in particular BBB-permeability characteristics, and since we have previously shown that BBB localization is disturbed by tumors, embolism, and mannitol injection, we investigated BBB-liposome permeability in an EAE rat model. Twenty young 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 permeability and liposome localization, radioactive liposomes and, 1 h later, 99mTc-DTPA were injected intravenously. Scintigraphic acquisitions were obtained to follow the biodistribution of radioactivity in the whole body. Each rat was subjected to a first examination before inoculation and then every two days until completion and may be considered as its own control. EAE induced 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 different disease stages in clinically patent EAE. The index of disease progression 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.