ArticleJournal of neuroinflammation2019
Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with spinal cord injury.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 140 citations in OpenAlex.
- 6-gingerol Attenuates Inflammatory Response in Rats With Spinal Cord Injury by Reducing NLRP3-mediated Microglial Pyroptosis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Astragaloside IV mitigates mitochondrial damage and neurological symptoms in rats with cervical spondylotic myelopathy by inhibiting IL-17/TRAF6/NF-κB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Varenicline-mediated cholinergic activation through α4β2 nAChR inhibits microglial neuroinflammation and alleviates neuropathic pain and depression following spinal cord injury.Journal of translational medicine · 2026Article
- Drp1-Dependent Mitochondrial Fission in the Hippocampus Drives Chronic Stress-Induced Depressive-like Behaviors in Mice.International journal of molecular sciences · 2026Article
- Neuroprotective Role of THBS2 in Experimental Spinal Cord Injury Via its Anti-neuroinflammatory and Anti-apoptotic Properties.Biochemical genetics · 2026Article
- Meningeal macrophages alleviate social memory defects in an early Alzheimer's disease model.Molecular psychiatry · 2026Article
- Limosilactobacillus reuteri DSM17938 Attenuates Neuroinflammatory Responses After Spinal Cord Injury by Modulating Tryptophan Metabolism.Probiotics and antimicrobial proteins · 2026Article
- Dnmt1 Alleviates S1PR1-Mediated Pyroptosis after Spinal Cord Injury through Regulating Pon3 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Quercetin targets the Ccl4-Ccr5 axis to relieve neuropathic pain after spinal cord injury.APL bioengineering · 2025Article
- The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.The journal of spinal cord medicine · 2025Article
- TCF7L2 regulates GPX4 to resist ferroptosis and enhance osteogenesis in mouse mesenchymal stem cells.European journal of medical research · 2025Article
- Uptake of DU145 and LNCaP prostate cancer cell line derived extracellular vesicles is inversely correlated with blood-brain barrier integrity in vitro.Fluids and barriers of the CNS · 2025Article
- Dusp1 in osteolytic diseases-mechanisms and therapeutic potential.Scientific reports · 2025Article
- TRIM55 suppresses inflammatory response after spinal cord injury by accelerating the ubiquitination and degradation of TLR4.Journal of orthopaedic surgery and research · 2025Article
- Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.Cellular and molecular neurobiology · 2025Review
- Ganoderma lucidum polysaccharide attenuates retinal ischemia-reperfusion injury by regulating microglial M1/M2 polarization, suppressing neuroinflammation and inhibiting JAK2/STAT3 pathway.Biochemistry and biophysics reports · 2025Article
- ISRIB facilitates post-spinal cord injury recovery through attenuation of neuronal apoptosis and modulation of neuroinflammation.Journal of orthopaedic translation · 2025Article
- Ghrelin Induces Ferroptosis Resistance and M2 Polarization of Microglia to Alleviate Neuroinflammation and Cognitive Impairment in Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions.Frontiers in immunology · 2025Review
- Interleukin-3 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair.CNS neuroscience & therapeutics · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe prognosis of spinal cord injury (SCI) is closely related to secondary injury, which is dominated by neuroinflammation. There is evidence that α-synuclein aggregates after SCI and that inhibition of α-synuclein aggregation can improve the survival of neurons after SCI, but the mechanism is still unclear. This study was designed to investigate the effects of α-synuclein on neuroinflammation after SCI and to determine the underlying mechanisms.
methodA T3 spinal cord contusion model was established in adult male Sprague-Dawley rats. An SNCA-shRNA-carrying lentivirus (LV-SNCA-shRNA) was injected into the injury site to block the expression of α-synuclein (forming the SCI+KD group), and the SCI and sham groups were injected with an empty vector. Basso-Beattie-Bresnahan (BBB) behavioural scores and footprint analysis were used to detect motor function. Inflammatory infiltration and myelin loss were measured in the spinal cord tissues of each group by haematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining, respectively. Immunohistochemistry, Western blot analysis, and RT-qPCR were used to analyse protein expression and transcription levels in the tissues. Immunofluorescence was used to determine the morphology and function of glial cells and the expression of matrix metalloproteinase-9 in the central canal of the spinal cord. Finally, peripheral serum cytokine levels were determined by enzyme-linked immunosorbent assay.
resultsCompared with the SCI group, the SCI+KD group exhibited reduced inflammatory infiltration, preserved myelin, and functional recovery. Specifically, the early arrest of α-synuclein inhibited the pro-inflammatory factors IL-1β, TNF-α, and IL-2 and increased the expression of the anti-inflammatory factors IL-10, TGF-β, and IL-4. The neuroinflammatory response was regulated by reduced proliferation of Iba1+ microglia/macrophages and promotion of the shift of M1-polarized Iba1+/iNOS+ microglia/macrophages to M2-polarized Iba1+/Arg1+ microglia/macrophages after injury. In addition, compared with the SCI group, the SCI+KD group also exhibited a smaller microglia/astrocyte (Iba1/GFAP) immunostaining area in the central canal, lower MMP-9 expression, and improved cerebrospinal barrier function.
conclusionLentivirus-mediated downregulation of α-synuclein reduces neuroinflammation, improves blood-cerebrospinal barrier function, promotes functional recovery, reduces microglial activation, and promotes the polarization of M1 microglia/macrophages to an M2 phenotype to confer a neuroprotective immune microenvironment in rats with SCI.
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