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

Abstract

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.

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F2Cross of Selectively-Bred Rats

“…In addition to this anti-inflammatory role, Mfge8 also plays a protective role in regulating adult stem cell populations (Y. Zhou et al, 2018) and is neuroprotective under a variety of injury and inflammatory states (e.g., stroke, prion diseases, neurodegeneration, brain injury (Chen et al, 2019; Choi et al, 2020; Gao et al, 2021; Kranich et al, 2010; Li et al, 2019; Qiu et al, 2022; J. Wang et al, 2021; Xiao et al, 2018).…”

The Critical Role of Sirt1 in Subarachnoid Hemorrhages: Mechanism and Therapeutic Considerations

“…After a SAH, HMGB1, released from necrotic neurons, could induce cytokine release and leukocyte recruitment and then trigger the inflammatory response after interaction with TLR4 and the receptor for advanced glycation end products (RAGEs) [ 69 ]. Experimental animal studies have revealed that the inhibition of HMGB1 could mitigate an inflammatory response and ameliorate EBI after a SAH [ 70 , 71 , 72 ]. Moreover, clinical research suggests that the serum HMGB1 of SAH patients may serve as an independent biomarker predictive of DCI [ 73 ].…”

Neuroinflammation and subarachnoid hemorrhage: a revised look at the literature

“…Milk fat globule epidermal growth factor 8 (MFG-E8) is a glycoprotein which mediates phagocytosis of apoptotic cells [ 29 ], that has recently been implicated in diminishing the inflammatory response [ 30 ]. One recent study employed the use of a recombinant MFG-E8 in a SAH rat model and discovered that MFG-E8 downregulated the proinflammatory HMGB1 and attenuated early brain injury caused by subarachnoid hemorrhage (SAH) [ 31 ]. Indeed, targeting the proinflammatory HMGB1 is a focus of recent work and has been shown to diminish early brain injury following SAH [ 32 , 33 ].…”