Valproic Acid Inhibits Endoplasmic Reticulum Stress and Reduces Ferroptosis After Traumatic Brain Injury.

BACKGOUND

Traumatic brain injury (TBI) is a severe neurological disorders, which invloving complicated molecular mechanisms, such as endoplasmic reticulum (ER) stress and ferroptosis. , However, the mechanism underlying TBI remains unclear.

OBJECTIVES

The Objective was to determine the effect of VPA on ER stress and ferroptosis, and affirm the relationship between ER stress and ferroptosis. Methods: The expression levels of GRP78, ATF6, CHOP and GPX4 in brain tissues were detected via western blot, histological staining, and immunofluorescence. The effect of VPA on ER stress and ferroptosis on OS cellswas evaluated in vitro and in vivo.

RESULTS

In our study, we found that VPA suppressed ER stress after TBI by inhibiting the GRP78-ATF6-CHOP signaling pathway, which ameliorated ferroptosis by reversing the reduction of the ferroptosis protein GPX4. Furthermore, tissue defects, bleeding, and iron accumulation also reduced. Moreover, 4-phenylbutyric acid was used to further confirm our assumption.

CONCLUSION

VPA plays a neuroprotective role by inhibiting ER stress levels and subsequently inhibiting ferroptosis.