Sult2b1 Modulates NLRP3/BCL-2 Signaling and Pro-Inflammatory Microglial/Macrophage Polarization After Traumatic Brain Injury
Hao Zhang, Zhenhong Pan, Hua Chen, Yinxing Huang, Shousen WangIntroduction:
Traumatic Brain Injury (TBI) causes prolonged neurological impairment through primary mechanical damage and secondary cascades including neuroinflammation and apoptosis. This study investigated whether Sult2b1, a cholesterol sulfation enzyme, protects against secondary injury after TBI.
Methods:
A Controlled Cortical Impact (CCI) mouse model was used. Sult2b1 expression was assessed by RT-qPCR and western blotting. AAV-mediated delivery restored Sult2b1, and its effects were evaluated via histology, immunofluorescence, imaging, ELISA, and behavioral tests.
Results:
Sult2b1 was markedly downregulated after TBI. Overexpression improved cerebral blood flow, preserved neurons, reduced apoptosis, decreased TNF-α and IL-1β, and increased IL-4. Mechanistically, it modulated NLRP3/BCL-2 and suppressed M1-like microglial/macrophage polarization. Functionally, it enhanced sensorimotor and cognitive performance and reduced lesion volume and chronic tissue loss.
Discussion:
Our findings identify Sult2b1 as an endogenous protective factor that limits neuroinflammation and promotes neuronal survival via NLRP3/BCL-2 and microglial polarization modulation, suggesting therapeutic potential.
Conclusion:
Sult2b1 confers neuroprotection after TBI and may serve as a potential target for reducing secondary brain injury.