The Protective Effects of the Triggering Receptor Expressed on Myeloid Cells-1 Inhibitor LP17 on Experimental Acute Brain Injury: A Systematic Review and Meta-Analysis Based on Animal Models

Abstract

Acute brain injury (ABI) is a severe neurological disorder in which inflammation and immune responses play a key role, with the Triggering Receptor Expressed on Myeloid Cells-1 (TREM1) being involved. Inhibition of TREM1 can alleviate neuroinflammation and damage, but the evidence from these pre-clinical studies remains unclear. This study summarizes and evaluates the results of animal experiments on the treatment of ABI with the TREM1 inhibitor LP17, exploring the effects of using LP17 to treat ABI animal models on neurological function, inflammatory indicators, and brain barrier function. As of April 30, 2025, this review conducted a detailed search of eight databases for studies on LP17 in ABI animal models. It performed a systematic review and meta-analysis of the included studies. The literature was independently screened, and data were extracted and assessed. RevMan 5.4 software was used for the meta-analysis. Compared with controls, the TREM1 inhibitor LP17 significantly reduced brain water content (standardized mean difference [SMD]: −1.36; 95% confidence interval [CI]: −1.77, −0.94; p < 0.00001) and neurological deficit scores (SMD: −1.37; 95% CI: −1.76, −0.97; p < 0.00001). It also decreased the expression of pro-inflammatory cytokines, including IL-1β (SMD: −1.88; 95% CI: −2.63, −1.13; p < 0.00001) and TNF-α (SMD: −2.91; 95% CI: −3.89, −1.92; p < 0.00001). LP17 mitigated blood–brain barrier (BBB) disruption (SMD: −1.58; 95% CI: −2.47, −0.68; p = 0.0005) and enhanced ZO-1 expression (SMD: 2.77; 95% CI: 1.73, 3.80; p < 0.00001). It also inhibited the activation of nuclear factor-κB (SMD: −1.70; 95% CI: −2.58, −0.83; p = 0.0001), NLRP3 (SMD: −2.33; 95% CI: −3.27, −1.39; p < 0.00001), and Caspase-1 (SMD: −2.03; 95% CI: −2.92, −1.14; p < 0.00001). LP17 has neuroprotective effects in ABI animal models, likely through reducing neuroinflammation, preserving BBB integrity, and inhibiting apoptotic pathways. Further studies are needed to explore its mechanisms to better guide clinical use.