MK5 Regulates Microglial Activation and Neuroinflammation in Experimental Stroke Models

Area of Science:

• Neuroscience
• Immunology
• Molecular Biology

Background:

• Microglial activation is central to neuroinflammation following ischemic stroke.
• Understanding the molecular mechanisms governing microglial responses is crucial for developing effective stroke therapies.

Purpose of the Study:

• To investigate the role of MK5 in microglial cells during the inflammatory response to ischemic stroke.
• To elucidate the potential mechanisms underlying MK5's function in neuroinflammation.

Main Methods:

• Utilized microglia-specific conditional MK5 knockout (MK5 cKO) mice and BV2 microglial cells.
• Induced ischemic conditions using middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation/reperfusion (OGD/R) in vitro.
• Assessed neurological deficits, infarct volume, inflammatory markers, microglial activation, and protein phosphorylation (HSP27, NF-κB).

Main Results:

• MK5 knockout exacerbated neurological deficits and infarct volume in MCAO mice.
• Loss of MK5 enhanced pro-inflammatory responses and microglial activation in both in vivo and in vitro models.
• MK5 deficiency reduced HSP27 phosphorylation and increased NF-κB phosphorylation.

Conclusions:

• Microglial MK5 plays a critical role in regulating the ischemic neuroinflammatory response.
• MK5 influences neuroinflammation by modulating HSP27 and NF-κB phosphorylation.
• MK5 represents a potential therapeutic target for treating ischemic stroke.