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Neurotherapeutics

, Volume 7, Issue 4, pp 378–391 | Cite as

Microglial activation in stroke: Therapeutic targets

  • Midori A. Yenari
  • Tiina M. Kauppinen
  • Raymond A. SwansonEmail author
Review Article

Summary

Microglial activation is an early response to brain ischemia and many other Stressors. Microglia continuously monitor and respond to changes in brain homeostasis and to specific signaling molecules expressed or released by neighboring cells. These signaling molecules, including ATP, glutamate, cytokines, prostaglandins, zinc, reactive oxygen species, and HSP60, may induce microglial proliferation and migration to the sites of injury. They also induce a nonspecific innate immune response that may exacerbate acute ischemic injury. This innate immune response includes release of reactive oxygen species, cytokines, and proteases. Microglial activation requires hours to days to fully develop, and thus presents a target for therapeutic intervention with a much longer window of opportunity than acute neuroprotection. Effective agents are now available for blocking both microglial receptor activation and the microglia effector responses that drive the inflammatory response after stroke. Effective agents are also available for targeting the signal transduction mechanisms linking these events. However, the innate immune response can have beneficial as well deleterious effects on outcome after stoke, and a challenge will be to find ways to selectively suppress the deleterious effects of microglial activation after stroke without compromising neurovascular repair and remodeling.

Key Words

NF-κB AP-1 PARP-1 minocycline inflammation ischemia TREM2 

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Copyright information

© Springer 2010

Authors and Affiliations

  • Midori A. Yenari
    • 1
  • Tiina M. Kauppinen
    • 1
  • Raymond A. Swanson
    • 1
    Email author
  1. 1.Department of NeurologyUniversity of California San Francisco and San Francisco Veterans Affairs Medical CenterSan Francisco

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