Soluble TREM2 ameliorates pathological phenotypes in ischemic stroke models via modulating neuronal and microglial...

Area of Science:

• Neuroscience
• Immunology
• Molecular Biology

Background:

• Triggering receptor expressed on myeloid cell 2 (TREM2) upregulation shows neuroprotection in ischemic stroke.
• The role and levels of soluble TREM2 (sTREM2) in ischemic stroke are currently unknown.

Purpose of the Study:

• To investigate the changes in sTREM2 levels and its functional effects in ischemic stroke.
• To determine the impact of sTREM2 on neuronal survival and brain injury.

Main Methods:

• Used oxygen-glucose deprivation (OGD) in neuron-microglia co-cultures and a transient middle cerebral artery occlusion (tMCAO) mouse model.
• Analyzed sTREM2 levels, its effect on nNOS-PSD-95 interaction via co-immunoprecipitation, and microglial activation through immunohistochemistry.
• Quantified gene expression of TREM2, IL-4, and IL-13 using qRT-PCR.

Main Results:

• sTREM2 levels decreased after OGD and tMCAO.
• sTREM2 reduced neuronal death in OGD and alleviated brain infarction and neurological deficits in tMCAO.
• sTREM2 disrupted nNOS-PSD-95 interaction, promoted microglial activation, and increased anti-inflammatory cytokine expression.

Conclusions:

• sTREM2 plays a protective role against transient cerebral ischemia.
• sTREM2 exerts neuroprotection by modulating neuronal and microglial responses.
• This study is the first to demonstrate the protective effects of sTREM2 in ischemic stroke.