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Published on: November 9, 2020
Inosine Ameliorates the Injurious Microenvironment for Oligodendrocyte Precursor Cells by Suppressing Microglial
Yong Han1, Jin Chen1, Peilian Wang1
1Department of Human Anatomy and Histoembryology, Basic Medical College of Ningxia Medical University, Yinchuan, 750004, Ningxia, P.R. China.
Neurochemical Research
|May 20, 2026
Summary
Inosine directly reduces microglial inflammation by inhibiting the TLR4/MyD88/NF-κB pathway. This protects oligodendrocyte precursor cells (OPCs) from damage, offering neuroprotection against neonatal white matter injury (WMI).
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Neonatal white matter injury (WMI) is a primary cause of cerebral palsy, linked to microglial-driven neuroinflammation.
- Microglial activation impairs oligodendrocyte precursor cell (OPC) survival and differentiation.
- Inosine's in vivo neuroprotective effects against WMI are known, but its direct impact on microglia requires elucidation.
Purpose of the Study:
- To investigate the direct effects of inosine on microglial activation and inflammatory responses in vitro.
- To determine if inosine modulates the TLR4/MyD88/NF-κB signaling pathway in microglia.
- To assess the impact of inosine-modulated microglia on OPC viability, proliferation, and differentiation.
Main Methods:
- Primary microglia were stimulated with lipopolysaccharide (LPS) and treated with inosine.
- Cytokine secretion (TNF-α, IL-1β, IL-6) and TLR4 pathway protein expression were measured.
- Microglia-conditioned medium (MCM) was applied to OPC cultures to evaluate OPC viability, apoptosis, proliferation, and differentiation.
Main Results:
- Inosine significantly reduced LPS-induced secretion of TNF-α, IL-1β, and IL-6 from microglia.
- Inosine downregulated the expression of TLR4, MyD88, and p-NF-κB p65 in microglia.
- MCM from inosine-treated microglia enhanced OPC viability, reduced apoptosis, increased proliferation, and promoted differentiation.
Conclusions:
- Inosine directly inhibits microglial overactivation and inflammation in vitro via TLR4/MyD88/NF-κB pathway downregulation.
- Inosine indirectly protects OPCs by mitigating the detrimental effects of activated microglia.
- These findings provide cellular mechanisms for inosine's neuroprotective role in neonatal WMI.
