Related Experiment Video
Updated: May 15, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice following
Matthias W Sieber1, Nadine Jaenisch, Martin Brehm
1Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Background:
Triggering receptor expressed on myeloid cells-2 (TREM2) is a microglial surface receptor involved in phagocytosis. Clearance of apoptotic debris after stroke represents an important mechanism to re-attain tissue homeostasis and thereby ensure functional recovery. The role of TREM2 following stroke is currently unclear.
Methods And Results:
As an experimental stroke model, the middle cerebral artery of mice was occluded for 30 minutes with a range of reperfusion times (duration of reperfusion: 6 h/12 h/24 h/2 d/7 d/28 d). Quantitative PCR (qPCR) revealed a greatly increased transcription of TREM2 after stroke. We subsequently analyzed the expression of pro-inflammatory cytokines, chemokines and their receptors in TREM2-knockout (TREM2-KO) mice via qPCR. Microglial activation (CD68, Iba1) and CD3-positive T-cell invasion were analyzed via qPCR and immunohistochemistry. Functional consequences of TREM2 knockout were assessed by infarct volumetry. The acute inflammatory response (12 h reperfusion) was very similar between TREM2-KO mice and their littermate controls. However, in the sub-acute phase (7 d reperfusion) following stroke, TREM2-KO mice showed a decreased transcription of pro-inflammatory cytokines TNFα, IL-1α and IL-1β, associated with a reduced microglial activity (CD68, Iba1). Furthermore, TREM2-KO mice showed a reduced transcription of chemokines CCL2 (MCP1), CCL3 (MIP1α) and the chemokine receptor CX3CR1, followed by a diminished invasion of CD3-positive T-cells. No effect on the lesion size was observed.
Conclusions:
Although we initially expected an exaggerated pro-inflammatory response following ablation of TREM2, our data support a contradictory scenario that the sub-acute inflammatory reaction after stroke is attenuated in TREM2-KO mice. We therefore conclude that TREM2 appears to sustain a distinct inflammatory response after stroke.
Insights
Triggering receptor expressed on myeloid cells-2 (TREM2) plays a role in the brain's inflammatory response after stroke. TREM2 knockout mice showed reduced inflammation and immune cell activity in the sub-acute phase, suggesting TREM2 sustains this response.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Triggering receptor expressed on myeloid cells-2 (TREM2) is a microglial surface receptor crucial for phagocytosis.
- Efficient clearance of apoptotic debris post-stroke is vital for tissue homeostasis and functional recovery.
- The specific role of TREM2 in the context of ischemic stroke remains largely undefined.
Purpose of the Study:
- To investigate the function of TREM2 in the inflammatory response following experimental stroke.
- To determine the impact of TREM2 deficiency on microglial activation, immune cell infiltration, and lesion development after stroke.
Main Methods:
- An experimental stroke model was established using middle cerebral artery occlusion in mice.
- TREM2 knockout (TREM2-KO) mice and littermate controls were subjected to varying reperfusion times.
- Quantitative PCR (qPCR), immunohistochemistry, and infarct volumetry were employed to assess gene expression, cellular activity, and lesion size.
Main Results:
- TREM2 transcription was significantly upregulated following stroke in wild-type mice.
- TREM2-KO mice exhibited attenuated pro-inflammatory cytokine and chemokine transcription in the sub-acute phase (7 days post-stroke).
- Reduced microglial activation (CD68, Iba1) and diminished CD3-positive T-cell invasion were observed in TREM2-KO mice, without affecting infarct volume.
Conclusions:
- Contrary to initial expectations, TREM2 deficiency led to an attenuated sub-acute inflammatory reaction post-stroke.
- These findings suggest that TREM2 actively sustains a specific inflammatory response following ischemic injury.
- TREM2 modulation may represent a potential therapeutic target for managing post-stroke inflammation.
