Blood-brain barrier integrity and glial support

Mechanisms that can be targeted for novel therapeutic approaches in stroke

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The blood-brain barrier (BBB) is a critical regulator of brain homeostasis. Additionally, the BBB is the most significant obstacle to effective CNS drug delivery. It possesses specific charcteristics (i.e., tight junction protein complexes, influx and efflux transporters) that control permeation of circulating solutes including therapeutic agents. In order to form this "barrier," brain microvascular endothelial cells require support of adjacent astrocytes and microglia. This intricate relationship also occurs between endothelial cells and other cell types and structures of the CNS (i.e., pericytes, neurons, extracellular matrix), which implies existence of a "neurovascular unit." Ischemic stroke can disrupt the neurovascular unit at both the structural and functional level, which leads to an increase in leak across the BBB. Recent studies have identified several pathophysiological mechanisms (i.e., oxidative stress, activation of cytokinemediated intracellular signaling systems) that mediate changes in the neurovascular unit during ischemic stroke. This review summarizes current knowledge in this area and emphasizes pathways (i.e., oxidative stress, cytokine-mediated intracellular signaling, glial-expressed receptors/targets) that can be manipulated pharmacologically for i) preservation of BBB and glial integrity during ischemic stroke and ii) control of drug permeation and/or transport across the BBB. Targeting these pathways present a novel opportunity for optimization of CNS delivery of therapeutics in the setting of ischemic stroke.

Original languageEnglish (US)
Pages (from-to)3624-3644
Number of pages21
JournalCurrent Pharmaceutical Design
Volume18
Issue number25
DOIs
StatePublished - 2012

Fingerprint

Blood-Brain Barrier
Neuroglia
Stroke
Oxidative Stress
Endothelial Cells
Tight Junction Proteins
Therapeutics
Pericytes
Drug and Narcotic Control
Brain
Microglia
Astrocytes
Extracellular Matrix
Homeostasis
Cytokines
Neurons
Pharmaceutical Preparations

Keywords

  • Astrocyte
  • Blood-brain barrier
  • Drug delivery
  • Endothelial cell
  • Ischemic stroke
  • Tight junction
  • Transporters

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

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