Microglia in ischemic brain injury

Jonathan R. Weinstein, Ines Koerner, Thomas Mller

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity.

Original languageEnglish (US)
Pages (from-to)227-246
Number of pages20
JournalFuture Neurology
Volume5
Issue number2
DOIs
StatePublished - Mar 2010

Fingerprint

Microglia
Brain Injuries
Stroke
Phenotype
Hypoxia-Inducible Factor 1
Ischemic Preconditioning
Toll-Like Receptor 4
Brain Ischemia
Transcriptome
Astrocytes
Neutrophils
Ischemia
Macrophages
T-Lymphocytes
Neurons
Brain
In Vitro Techniques

Keywords

  • Hypoxia inducible factor
  • Ischemia
  • Ischemic preconditioning
  • Microglia
  • Toll-like receptor

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Microglia in ischemic brain injury. / Weinstein, Jonathan R.; Koerner, Ines; Mller, Thomas.

In: Future Neurology, Vol. 5, No. 2, 03.2010, p. 227-246.

Research output: Contribution to journalArticle

Weinstein, JR, Koerner, I & Mller, T 2010, 'Microglia in ischemic brain injury', Future Neurology, vol. 5, no. 2, pp. 227-246. https://doi.org/10.2217/fnl.10.1
Weinstein, Jonathan R. ; Koerner, Ines ; Mller, Thomas. / Microglia in ischemic brain injury. In: Future Neurology. 2010 ; Vol. 5, No. 2. pp. 227-246.
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