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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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
StatePublished - 1986

Fingerprint

Blood-Brain Barrier
Immunoglobulin M
Monoclonal Antibodies
Brain
Capillary Permeability
Permeability
Thyroid Gland
Anesthesia
Pharmacokinetics
Antibodies

ASJC Scopus subject areas

  • Physiology

Cite this

Osmotic blood-brain barrier opening to IgM monoclonal antibody in the rat. / Neuwelt, E. A.; Minna, J.; Frenkel, E.; Barnett, P. A.; McCormick, C. I.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 250, No. 5, 1986.

Research output: Contribution to journalArticle

@article{6591d0af8e1d459e9254ad70e96d7eb3,
title = "Osmotic blood-brain barrier opening to IgM monoclonal antibody in the rat",
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.",
author = "Neuwelt, {E. A.} and J. Minna and E. Frenkel and Barnett, {P. A.} and McCormick, {C. I.}",
year = "1986",
language = "English (US)",
volume = "250",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Osmotic blood-brain barrier opening to IgM monoclonal antibody in the rat

AU - Neuwelt, E. A.

AU - Minna, J.

AU - Frenkel, E.

AU - Barnett, P. A.

AU - McCormick, C. I.

PY - 1986

Y1 - 1986

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0022549181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022549181&partnerID=8YFLogxK

M3 - Article

C2 - 3706572

AN - SCOPUS:0022549181

VL - 250

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5

ER -