Sult2b1 Modulates NLRP3/BCL-2 Signaling and Pro-Inflammatory Microglial/Macrophage Polarization After Traumatic Brain Injury.
TL;DR
The 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.
Abstract
INTRODUCTION 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.