ArticleCellular and molecular neurobiology2021
Tetramethylpyrazine Protects Blood-Spinal Cord Barrier Integrity by Modulating Microglia Polarization Through Activation of STAT3/SOCS3 and Inhibition of NF-кB Signaling Pathways in Experimental Autoimmune Encephalomyelitis Mice.
Article in Cellular and molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 43 citations in OpenAlex.
- A2 astrocyte polarization mediates ketogenic diet protection of blood-central nervous system barriers in experimental autoimmune encephalomyelitis.Neural regeneration research · 2026Article
- Catalpol and tetramethylpyrazine relieve Alzheimer's disease by facilitating AQP4 protein expression and polarized distribution in hippocampal astrocytes via inducing the STAT3-mediated UCHL1 expression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Exercise training promotes nerve cell repair and regeneration after spinal cord injury.Neural regeneration research · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- Regulation of microglial polarization via notch signaling pathway by intrathecal administration of tanshinone IIA-PLGA sustained-release microspheres to promote neurological recovery after spinal cord injury.Frontiers in bioengineering and biotechnology · 2026Article
- The neuro-immuno-metabolic axis of exercise: a unified mechanistic framework for exercise-induced cognitive enhancement and psychological resilience.Frontiers in psychology · 2026Review
- Engineering a targeted daphnetin delivery system to enhance spinal cord injury treatment effectiveness.Materials today. Bio · 2025Article
- Sex- and age- differences in the expression of critical blood-brain barrier regulators: a physiological context.Biology of sex differences · 2025Article
- Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis.Brain sciences · 2025Review
- Runx2 Suppresses Astrocyte Activation and Astroglial Scar Formation After Spinal Cord Injury in Mice.Molecular neurobiology · 2024Article
- MFG-E8 Ameliorates Nerve Injury-Induced Neuropathic Pain by Regulating Microglial Polarization and Neuroinflammation via Integrin β3/SOCS3/STAT3 Pathway in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Quantitative proteomics of the miR-301a/SOCS3/STAT3 axis reveals underlying autism and anxiety-like behavior.Molecular therapy. Nucleic acids · 2024Article
- Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases: a review.Molecular biology reports · 2024Review
- Tetramethylpyrazine inhibits ferroptosis in spinal cord injury by regulating iron metabolism through the NRF2/ARE pathway.Frontiers in pharmacology · 2024Article
- Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis.Pharmaceutical biology · 2023Article
- Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies.NeuroSci · 2022Review
- Article
- Microglia Polarization: A Novel Target of Exosome for Stroke Treatment.Frontiers in cell and developmental biology · 2022Review
- Microglia Polarization From M1 to M2 in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Metformin Therapy Attenuates Pro-inflammatory Microglia by Inhibiting NF-κB in Cuprizone Demyelinating Mouse Model of Multiple Sclerosis.Neurotoxicity research · 2021Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported that tetramethylpyrazine (TMP) alleviates experimental autoimmune encephalomyelitis (EAE) by decreasing glia activation. Activated microglia has been shown to mediate blood-spinal cord barrier (BSCB) disruption, which is a primary and continuous pathological characteristic of multiple sclerosis (MS). Therefore, in this study, we further investigated whether TMP protects the BSCB integrity by inhibition of glia activation to alleviate EAE. Extravasation of evans blue was used to detect the BSCB disruption. Tumor necrosis factor-α (TNF-α)/interlukine-1β (IL-1β) and interlukine-4 (IL-4)/interlukine-10 (IL-10) were determined by enzyme-linked immunosorbent assay. BV2 glial cells stimulated by interferon-γ (IFN-γ) were co-cultured with human brain microvascular endothelial cells to investigate the effect of TMP on the BSCB disruption. Flow cytometry was used to analyze the microglia phenotype. Western blot was performed to reveal the signaling pathways involved in the microglia activation. In this study, most importantly, we found that TMP protects the BSCB integrity by modulating microglia polarization from M1 phenotype to M2 phenotype through activation of STAT3/SOCS3 and inhibition of NF-кB signaling pathways. Moreover, TMP significantly preserves the tight junction proteins, reduces the secretion of pro-inflammatory cytokines (TNF-α, IL-1β) and increases the secretion of anti-inflammatory cytokines (IL-4, IL-10) from IFN-γ-stimulated BV2 microglia cells. Consequently, protection of the BSCB integrity leads to alleviation of clinical symptoms and demyelination in EAE mice. Therefore, TMP might be an effective therapeutic agent for cerebral disorders with BBB or BSCB disruption, such as ischemic stroke, MS, and traumatic brain injury.
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