MFGE8 decreased neuronal apoptosis and neuroinflammation to ameliorate early brain injury induced by subarachnoid hemorrhage through the inhibition of HMGB1

• Published in: Human & experimental toxicology 2022-01, Vol.41, p.9603271221093635-9603271221093635
• Main Authors: Qiu, Jiaoxue, Li, Wenna, Mu, Rutao, Wang, Lingling, Guo, Lei, Ma, Lili
• Format: Article
• Language: English
• Subjects: Aneurysm; Animals; Antigens, Surface - pharmacology; Apoptosis; Brain; Brain Injuries - pathology; Brain injury; Edema; Enzyme-linked immunosorbent assay; Epidermal Growth Factor - metabolism; Epidermal Growth Factor - pharmacology; Factor VIII - metabolism; Factor VIII - pharmacology; Glycolipids; Glycoproteins; Glycyrrhizin; Head injuries; Hemorrhage; HMGB1 protein; HMGB1 Protein - metabolism; HMGB1 Protein - pharmacology; Immunofluorescence; Inflammation; Lipid Droplets; Milk Proteins - metabolism; Milk Proteins - pharmacology; Moisture content; Neuroinflammatory Diseases; Rats; Rats, Sprague-Dawley; Signal Transduction; Staining; Subarachnoid hemorrhage; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - drug therapy; Subarachnoid Hemorrhage - metabolism; Ventricle (lateral); Water content
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/09603271221093635

Aim Both MFGE8 and HMGB1 were vital players for aneurysmal subarachnoid hemorrhage. However, whether HMGB1 was served as the downstream target of MFGE8 was unknown. To test this new mechanism, we performed the SAH model in rats. Method All treatments were injected intraventricularly into the right lateral ventricles. SAH grade, brain water content, and neurological function scores were evaluated. HMGB1 expression was studied by double immunofluorescence staining. HE and Nissl’s staining were performed to observe the pathological change. Inflammatory factors were measured by ELISA method. Results High expression of MFGE8 could improve neurological function and reduce the brain edema and pro-inflammatory factors. Injection of rhMFGE8 inhibited HMGB1. To further verify the regulation of MFGE8 in HMGB1, we used rhHMGB1 and glycyrrhizin, and the results indicated MFGE8 produced excellent effect on SAH rats via inhibiting HMGB1. Conclusion In a word, MFGE8 improved EBI caused by SAH, depending on HMGB1 that was the potential mechanism.