The Effect of Hyperosmotic Blood Brain Barrier Disruption on Experimental Autoimmune Encephalomyelitis
The blood brain barrier (BBB) plays a major role in maintaining the stable environment required for normal brain function. Several mechanisms are acting in concert to prevent the passage of polar and high molecular weight compounds or to actively transfer other compounds to the brain parenchyma. Pathological changes in brain permeability have been described in several conditions such as, poisoning (Rapoport, 1976), irradiation (Siegal and Pfeffer, 1975) and injury (Stahel et al.,2000) where the brain parenchyma and blood vessels are severely damaged. During cell mediated immune insults such as in multiple sclerosis (MS) and in its experimental counterpart, experimental autoimmune encephalomyelitis (EAE), the active infiltration of effector lymphocytes into the brain parenchyma is accompanied by a local and transient disruption of BBB (Silver et al.,1999). There is a tacit assumption that this change in BBB integrity during immune insults may contribute to the immunopathological process by attracting humoral and cellular effectors, thereby causing a propagation of the disease. Furthermore, in any tentative treatment suggested for the relief of the inflammation in the CNS, there is always the question, whether the drug penetrates the BBB so as to affect the cells within the brain parenchyma. The use of pharmacological means to disrupt the barrier, in order to deliver effective doses of immunosuppressive drugs into the CNS, was reluctantly unexplored mainly because of the concern that such treatment would aggravate an ongoing disease. In this study we have challenged this assumption by investigating the effect of a transient change in BBB on the outcome of an ongoing disease in the brain. To this aim we have tested the effect of hyperosmotic disruption of the BBB on the outcome of EAE in rats.
KeywordsMultiple Sclerosis Blood Brain Barrier Experimental Autoimmune Encephalomyelitis Brain Parenchyma Post Inoculation
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