Retinoic acid-inducible gene-I aggravates neuroinflammation in early brain injury after subarachnoid hemorrhage through mediating brain microvascular endothelial cell pyroptosis
Year: 2025
Type: article
Abstract: Retinoic acid-inducible gene-I (RIG-I) is an immune signal that promotes inflammatory responses and plays an important role in endothelial cell-mediated inflammation. Currently, no studies have investigated the role of RIG-I in early brain injury (EBI) after subarachnoid hemorrhage (SAH). In this research, an in vivo SAH model was established in Sprague Dawley (SD) rats through carotid artery puncture, while oxyhemoglobin (OxyHb) was used to stimulate brain microvascular endothelial cells (BMVECs) to generate an in vitro SAH model. The results showed that RIG-I was activated and expressed in BMVECs in both in vivo and in vitro. To explore how RIG-I is involved in the EBI, small interfering RNA was used to downregulate its expression. Compared with SAH rats, RIG-I knockdown rats had better short-term and long-term neurological recovery after SAH, milder brain edema and neurodegeneration, and weaker blood-brain barrier disruption and neuroinflammation. Furthermore, RIG-I knockdown attenuated SAH-induced BMVECs pyroptosis. In OxyHb-stimulated BMVECs, RIG-I knockdown reduced the cellular dysfunction and inflammation. To determine the mechanism of RIG-I in BMVECs pyroptosis, co-immunoprecipitation was used to verify the direct binding of RIG-I to caspase-1, and RIG-I knockdown could reduce Oxy-Hb-induced BMVECs pyroptosis, while caspase-1 inhibitor VX-765 can alleviate the tight junction loss, inflammation and pyroptosis exacerbated by RIG-I agonist. In addition, RIG-I levels in the cerebrospinal fluid of SAH patients were higher than those in controls and correlated with the levels of pyroptosis, inflammatory factors and clinical outcomes. In summary, the results demonstrated that RIG-I aggravates neuroinflammation after SAH by promoting caspase-1-mediated BMVECs pyroptosis.
Source: Neurotherapeutics
Authors: Bowen Sun, Yuchen Li, Shuai Lan, Xi-ao Wang, Yeping Ling, Harshal Sawant, Bohan Zhang, Jinshuo Yang, Jinju Wang, Pei Wu, Shancai Xu, Ji Bihl, Huaizhang Shi
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,900
Funders: Harbin Medical University, Postdoctoral Scientific Research Development Fund of Heilongjiang Province, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Natural Science Foundation of Heilongjiang Province, National Institutes of Health, Wu Jieping Medical Foundation, National Institute of General Medical Sciences
Awards: G1020720585, G1739031488, G1991326184, G2487870917, G3648083370, G4251628663, G4936840906, G5597112971, G5783365073, G8056481702, G8539814308, West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE), West Virginia Clinical and Translational Science Institute: A Statewide Organization Building Research Excellence and Engaging Communities to Improve Health
OpenAlex ID: W4409147369