ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2012
Effects of 2-chlorodeoxyadenosine (Cladribine) on primary rat microglia.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Impact of Oral Cladribine on TSPO-PET-Measurable Immune Cell Activation in Multiple Sclerosis.Neurology and therapy · 2026Article
- The effect of cladribine tablets on intrathecal inflammation in relapsing-remitting multiple sclerosis.Journal of neuroinflammation · 2026Article
- Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage.International journal of molecular sciences · 2025Article
- Microglial Mayhem NLRP3 Inflammasome's Role in Multiple Sclerosis Pathology.CNS neuroscience & therapeutics · 2024Review
- Towards Treating Multiple Sclerosis Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- Bioavailable central nervous system disease-modifying therapies for multiple sclerosis.Frontiers in immunology · 2023Review
- Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients.International journal of molecular sciences · 2022Article
- Central nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics.Journal of neuroinflammation · 2022Review
- Mechanism-based criteria to improve therapeutic outcomes in progressive multiple sclerosis.Nature reviews. Neurology · 2022Review
- Cladribine Treatment for MS Preserves the Differentiative Capacity of Subsequently Generated Monocytes, Whereas Its AdministrationFrontiers in immunology · 2022Article
- The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations.Frontiers in immunology · 2021Review
- The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review.Drugs · 2020Review
- Cladribine modifies functional properties of microglia.Clinical and experimental immunology · 2020Article
- Oral Therapies for Multiple Sclerosis.Cold Spring Harbor perspectives in medicine · 2019Review
- Review
- In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia.Journal of neuroinflammation · 2016Article
- The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.Scientific reports · 2015Article
- 2-Chlorodeoxyadenosine (cladribine) induces apoptosis in human monocyte-derived dendritic cells.Clinical and experimental immunology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
2-chlorodeoxyadenosine (CdA, Cladribine) is an immunosuppressant that has recently been shown to be effective in the treatment of multiple sclerosis (MS). There is extensive clinical experience with CdA for the treatment of neoplastic diseases, especially hematologic malignancies, due to its apoptotic effects on leukemic and several other neoplastic cells. Furthermore, CdA crosses the blood-brain-barrier and thus may also exert its effects directly on cells of the central nervous system (CNS). Therefore, we have studied the effects of CdA on cultured primary rat microglia, the resident macrophage in the CNS, which is also thought to be involved in the pathogenesis of MS. Treatment of microglia with CdA inhibited their proliferation and induced apoptosis. Phosphorylation of CdA to CdATP was required for both effects and was inhibited by deoxycytidine. Furthermore, activation of caspase-3 and -9 revealed the involvement of the intrinsic mitochondrial mediated apoptotic pathway. However, the absence of caspase-8 activation specified independency from the extrinsic death receptor mediated apoptosis. The mitochondrial membrane potential was significantly reduced after CdA exposure and was not conserved with Bax or caspase-3 inhibition. Assessment of DNA fragmentation by TUNEL and DNA-release-assay showed microglia with fragmented nuclei. Other functions of microglia like phagocytosis and LPS-induced NO and TNF-α release were not affected by CdA. These data suggest a potential of CdA treatment to induce not only leukopenia but also apoptosis in microglia in the CNS. These results help to understand the mechanism of action of CdA in CNS diseases and may open the possibility to target microglia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.