Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain

J. D. Huber, C. R. Campos, K. S. Mark, Thomas P Davis

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1-6 h); however, brain region-specific increases in microglial activation suggest a potential for a central-mediated response.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number2
DOIs
StatePublished - Feb 2006

Fingerprint

Carrageenan
Intercellular Adhesion Molecule-1
Blood-Brain Barrier
Pain
Brain
Cytokines
Proteins
Immunohistochemistry
RNA
Inflammation
Tight Junction Proteins
Parietal Lobe
Microglia
Frontal Lobe
Microvessels
Thalamus
Leukocyte Count
Opioid Analgesics
Permeability
Flow Cytometry

Keywords

  • Adhesion molecule
  • Intercellular adhesion molecule-1
  • Leucocyte transmigration
  • Neurovascular unit
  • Proinflammatory mediators

ASJC Scopus subject areas

  • Physiology

Cite this

@article{5062f5665c8e4a83a60fadd106458577,
title = "Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain",
abstract = "Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1-6 h); however, brain region-specific increases in microglial activation suggest a potential for a central-mediated response.",
keywords = "Adhesion molecule, Intercellular adhesion molecule-1, Leucocyte transmigration, Neurovascular unit, Proinflammatory mediators",
author = "Huber, {J. D.} and Campos, {C. R.} and Mark, {K. S.} and Davis, {Thomas P}",
year = "2006",
month = "2",
doi = "10.1152/ajpheart.00747.2005",
language = "English (US)",
volume = "290",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain

AU - Huber, J. D.

AU - Campos, C. R.

AU - Mark, K. S.

AU - Davis, Thomas P

PY - 2006/2

Y1 - 2006/2

N2 - Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1-6 h); however, brain region-specific increases in microglial activation suggest a potential for a central-mediated response.

AB - Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1-6 h); however, brain region-specific increases in microglial activation suggest a potential for a central-mediated response.

KW - Adhesion molecule

KW - Intercellular adhesion molecule-1

KW - Leucocyte transmigration

KW - Neurovascular unit

KW - Proinflammatory mediators

UR - http://www.scopus.com/inward/record.url?scp=33644869486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644869486&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00747.2005

DO - 10.1152/ajpheart.00747.2005

M3 - Article

C2 - 16199477

AN - SCOPUS:33644869486

VL - 290

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 2

ER -