ArticleJournal of inflammation research2020
Protective Effects of Leukadherin1 in a Rat Model of Targeted Experimental Autoimmune Encephalomyelitis (EAE): Possible Role of P47phox and MDA Downregulation.
Article in Journal of inflammation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 15 citations in OpenAlex.
- Lipid-coated mesoporous silica nanoparticles loaded with Thymoquinone as a novel treatment for experimental autoimmune encephalomyelitis in rats.BMC pharmacology & toxicology · 2026Article
- Antiseizure Effects of Mirtazapine in a Rat Model of Status Epilepticus Via Cannabinoid Receptor Modulation.Neurochemical research · 2025Article
- CD11b Activation Reduces Myeloid Brain Infiltration and Mitigates Synucleinopathy in a Model of Parkinson's Disease.bioRxiv : the preprint server for biology · 2025Article
- Dynamic Transcriptomic and Cellular Remodeling Underlie Cuprizone-Induced Demyelination and Endogenous Repair in the CNS.Antioxidants (Basel, Switzerland) · 2025Article
- Proteomic Profiling and Therapeutic Targeting of Oxidative Stress in Autoimmune Encephalitis.Journal of molecular neuroscience : MN · 2025Article
- Mechanosensitivity of macrophage polarization: comparing small molecule leukadherin-1 to substrate stiffness.Frontiers in immunology · 2025Article
- Effects of β-sitosterol on anxiety in migraine-induced rats: The role of oxidative/nitrosative stress and mitochondrial function.CNS neuroscience & therapeutics · 2024Article
- Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells.Chinese journal of integrative medicine · 2023Article
- Alteration of Glycerophospholipid Metabolism in Hippocampus of Post-stroke Depression Rats.Neurochemical research · 2022Article
- Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Gingival-Derived MSCs on Bleomycin-Induced Pulmonary Fibrosis in Mice.International journal of molecular sciences · 2021Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReactive oxygen and nitrogen species (ROS and RNS) are involved in pathologic mechanisms underlying demyelination and exacerbation in multiple sclerosis (MS) lesions. P47phox is the most important subunit of an ROS-producing enzyme (NADPH oxidase) which is reportedly upregulated in MS plaques due to the intense activity of infiltrated immune cells and resident microglia. Leukadherin1 is a specific CD11b/CD18 agonist that inhibits signaling and transmigration of inflammatory cells to sites of injury. Based on this mechanism, we evaluated therapeutic effects of leukadherin1 in an animal model of targeted experimental autoimmune encephalomyelitis (EAE) through focal injection of inflammatory cytokines to the spinal cord.
methodsFor model induction, Lewis rats were first immunized with 15µg MOG 1-125 emulsion. Twenty days later, animals were subjected to stereotaxic injection of IFNγ and TNFα to the specific spinal area (T8). One day after injection, all animals presented EAE clinical signs, and their behaviors were monitored for eight days through open-field locomotion and grid-walking tests. Leukadherin1-treated animals received daily intraperitoneal injections of 1mg/kg of the drug. The specific spinal tissues were extracted on day 5 in order to measure nitric oxide (NO), malon di-aldehyde (MDA), and TNFα concentrations alongside P47phox real-time PCR analysis. In addition, spinal sections were prepared for immunohistochemical (IHC) observation of infiltrated leukocytes and activated microglia.
resultsLeukadherin1 exhibited promising improvements in EAE clinical scores and behavioral tests. Demyelination, CD45+ leukocyte infiltration, and Iba1+ microglia activation were reduced in spinal tissues of leukadherin1-treated animals. Furthermore, P47phox expression levels, MDA, and NO amounts were decreased in treated animals. However, TNFα concentrations did not differ following treatment.
conclusionBased on our results, we suggest that leukadherin1 may be used as a novel therapeutic agent in tackling the clinical challenge of multiple sclerosis, especially during the acute phase of the disease. This effect was possibly mediated through decreased leukocyte infiltration and oxidative stress.
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