AUTHOR=Hu Yangchun , Li Chao , Wang Xiaojian , Chen Weiwei , Qian Yu , Dai Xingliang 

TITLE=TREM2, Driving the Microglial Polarization, Has a TLR4 Sensitivity Profile After Subarachnoid Hemorrhage

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.693342

DOI=10.3389/fcell.2021.693342

ISSN=2296-634X

ABSTRACT=<p>Increasing evidence suggests that triggering receptor expressed on myeloid cells 2 (<italic>TREM2</italic>) is implicated in the pathophysiology of neuroinflammation. The aim here was to investigate the neuroprotective role of <italic>TREM2</italic> and its regulatory mechanism after subarachnoid hemorrhage (SAH). <italic>TREM2</italic> siRNA was administered to measure the detrimental role of <italic>TREM2</italic> in mediating microglial polarization <italic>in vivo</italic> and <italic>in vitro</italic> after experimental SAH. The relationship between Toll-like receptor 4 (<italic>TLR4</italic>) signaling and <italic>TREM2</italic> was further explored. The soluble <italic>TREM2</italic> from the cerebrospinal fluid (CSF) of patients with SAH was detected. The results showed that <italic>TREM2</italic> mainly located in the microglia and presented a markedly delayed elevation after SAH. <italic>TREM2</italic> knockdown triggered increased pro-inflammatory productions, aggravated microglial activities, and further exacerbated neurological dysfunction after SAH. Significantly, <italic>TLR4</italic> knockout increased the expression of <italic>TREM2</italic>, accompanied by ameliorated neuroinflammation and improved neurological function. Corresponding to different clinical Hunt–Hess grades, obviously enhanced accumulation of soluble <italic>TREM2</italic> was detected in the CSF of patients with SAH. <italic>TREM2</italic> played a pivotal role in mediating microglial polarization after SAH, and the neuroprotective effect of <italic>TREM2</italic> might be potentially suppressed by the hyperactive <italic>TLR4</italic> in the early phase of SAH. Pharmacological targeting of <italic>TREM2</italic> may be a promising strategy for SAH therapy.</p>