Blood-brain barrier and DNA changes during the evolution of experimental allergic encephalomyelitis.

Abstract

Spinal cord and brain distribution spaces of 3H-mannitol (MW 182) and 14C-dextran (MW 60,000-90,000) were measured in rats during the development of EAE. These distribution spaces were used as indicators of the permeability of brain vasculature. This permeability was compared with appearance of neurological signs and cellular infiltration. Small-cell infiltration was compared with increase of tissue DNA concentration. Neurological deficit appeared on about the 8th day after induction and remained confined to spinal cord, never involving cerebrum. Neurological deficit, small-cell infiltration, a rise in mannitol and dextran distribution spaces and DNA elevation all first appeared at approximately the same time. Neurological deficit appeared in the caudal end of the cord and proceeded rostrally. Cellular infiltration, tracer distribution spaces and DNA increases followed the same pattern. Neither the ascending disease pattern nor other aspects of the disease were altered by the use of cerebral vs. spinal cord antigen or cervical vs. inguinal lymph node injection. The absolute increase in distribution spaces of mannitol was greater than dextran, indicating a correlation of increased vascular permeability with molecular size of the test tracer.