Cerebral Interferon Entry in Mice after Osmotic Alteration of Blood–Brain Barrier

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Abstract
Systemically administered interferon (IFN) is not readily detected in the central nervous system (CNS) due to the presence of the blood-brain barrier (BBB). A method of osmotic BBB alteration in a mouse model was established in this laboratory. IFN''s entry into the normal and osmotically altered brain after its intracarotid injection was investigated. Significant IFN levels (100-1,000 units) in the brain can be achieved by this method. The highest IFN activity was found in the brain hemisphere ipsilateral to the injection site within 20 min to 1 h after injection. IFN activity in the brain was detectable up to 4 h. Animals injected in this manner with murine IFN-.alpha./.beta. (MuIFN-.alpha./.beta.) and observed for a 6-month time interval showed no signs of neurological dysfunctions and resumed their normal activities. The therapeutic value of this method will be tested in a murine model of malignant glioma.