Mild traumatic brain injury (mTBI) originates from tensile injury of axons caused by rapid forces. ATPase phospholipid transporting 8A2 (ATP8A2) maintains membrane asymmetry, and its dysregulation leads to phosphatidylserine (PS) exposure. Neuronal injury induced by ATP8A2 mutation or knockout resembles the pathological phenotype of mTBI, indicating its involvement in the pathological process of mTBI. Given that the PS/MFG-E8/VNR pathway mediates microglial phagocytosis, this study aimed to investigate whether blocking VNR can alleviate mTBI-induced synaptic loss and cognitive impairments, and clarify the underlying mechanism. We induced traumatic brain injury (TBI) in C57BL/6J mice using a weight-drop model, assessed neurological function by neurological deficit scoring (NSS) at 4 h, 1 day and 3 days after injury, and detected brain edema, neuroinflammation, pathological changes and by brain water content measurement, ELISA, HE staining, immunofluorescence and Western blotting. Cerebral edema, neuroinflammation, pathological changes and ATP8A2, microglia and synapse-related proteins were detected by ELISA, HE staining, immunofluorescence and Western blotting. Blocking the VNR receptor altered the outcomes of synaptic loss and cognitive behavioral abnormalities, but did not change the result of increased inflammatory factor levels in the prefrontal cortex. Blocking the PS/MFG-E8/VNR pathway promotes cognitive functional recovery in mTBI model mice by inhibiting microglial phagocytosis of synapses in the prefrontal cortex.
Li et al. (Sun,) studied this question.