Osmotic blood-brain barrier opening to IgM monoclonal antibody in the rat

Edward Neuwelt, J. Minna, E. Frenkel, P. A. Barnett, C. I. McCormick

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Abstract

Pharmacokinetic parameters of iodinated monoclonal antibody (MAb) delivery to normal rat brain were examined. The mean cerebrovascular permeability-surface area (PA; permeability x capillary surface area) to immunoglobulin M (IgM) MAb (mol wt 1,000,000) 10 min after infusion was 0.40 x 10-6 s-1. When osmotic blood-brain barrier (BBB) disruption is utilized, the PA increased to 8.36 x 10-6 s-1. Neither intravenous nor intracarotid MAb administration significantly affected delivery to brain. However, osmotic BBB opening significantly (P <0.0005) increased MAb uptake independent of the route of administration. After BBB opening and intracarotid MAb the maximum concentration in brain at 1 h was 0.72% per gram of the total administered dose. For 6 h postdisruption, ipsilateral brain levels were 25- to 100-fold greater than in the contralateral hemisphere or nonbarrier-disrupted controls. MAb concentration in brain slightly decreased over 72 h (P <0.05). Antibody recovered from disrupted brain retained 90% of its immunological reactivity for at least 24 h. MAb delivery to ipsilateral brain after BBB disruption was linear over a dose of 0.5-5.0 μg IgM, whereas the percentage of the total administered dose remained unchanged. After osmotic treatment, barrier opening was maximal to MAb delivery for 1 min with delivery declining rapidly thereafter. The type of anesthesia used and the administration of a thyroid-blocking agent were found to affect brain MAb levels after BBB disruption.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume250
Issue number5
Publication statusPublished - 1986

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ASJC Scopus subject areas

  • Physiology

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