Imagine you’re a firefighter tasked with extinguishing a blaze. But instead of water, you have TREM2, a powerful fire suppressant! Neuroinflammation is like the fire that can cause further damage after a brain hemorrhage. Luckily, TREM2 comes to the rescue by suppressing this inflammation and protecting the brain. Recent research used mouse models and cell cultures to explore TREM2’s neuroprotective role in intracerebral hemorrhage (ICH). The study found that increasing TREM2 expression improved neurological function, reduced neuroinflammation, and prevented neuronal death and brain swelling. How did TREM2 accomplish all this? It turns out that it inhibits Toll-like receptor 4 (TLR4) signaling, which plays a crucial role in activating inflammatory processes. By interfering with TLR4, TREM2 effectively dampened inflammation and prevented further damage. These findings shed light on the potential of targeting TREM2 to mitigate early brain injury following ICH. So, if you’re curious about how TREM2 could be utilized to protect the brain from neuroinflammation after hemorrhage, dive into the underlying research!

Neuroinflammation contributes to secondary brain injury following intracerebral hemorrhage (ICH). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effect by suppressing neuroinflammatory response in experimental ischemic stroke. This study aimed to clarify the neuroprotective role of TREM2 and potential underlying mechanism in a mouse model of ICH and in vitro. Adeno-associated virus (AAV) and green fluorescent protein-lentivirus (GFP-LV) strategies were employed to enhance TREM2 expression in the C57/BL6 mice and BV2 cells, respectively. The adult male C57/BL6 mice were subjected to ICH by administration of collagenase-IV in 1 month after the AAV particles injection. An in vitro ICH model was performed with oxygen hemoglobin in BV2 cells. Toll-like receptor 4 (TLR4) antagonist TAK242 was applied at 6 h following ICH. Neurological function, TREM2, pro-inflammatory cytokines, brain water content and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were evaluated at 24 h following ICH. TLR4, NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways were also determined by Western blot analysis at the same time point. The levels of TREM2 were increased at 12 h, peaked at 24 h and recovered on 7d following ICH. TREM2 overexpression ameliorated ICH induced neurological dysfunction, inhibited neuroinflammation, and attenuated apoptosis and brain edema. Further mechanistic study revealed that TREM2 overexpression inhibited TLR4 activation and NF-κB and MAPK signaling pathways. ICH increased the percentage of TUNEL-positive cells, which was markedly decreased by TREM2 overexpression. A similar improvement was also observed by the administration of TAK242 following ICH. TREM2 improves neurological dysfunction and attenuates neuroinflammation and neuronal apoptosis in the acute phase of ICH, which is, at least in part, mediated by negatively regulating TLR4 signaling pathway. These findings highlight TREM2 as a potential target for early brain injury following ICH.

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