ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Thrombin-induced microglial activation produces degeneration of nigral dopaminergic neurons in vivo.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 161 citations in OpenAlex.
- Ursodeoxycholic acid mitigates cerebral ischemia/reperfusion injury by inhibiting thrombin-induced lipid peroxidation through activation of ALDH3A1.Redox biology · 2026Article
- Therapeutic targeting of blood-derived protein infiltration to modulate neuroinflammation in cerebellar ataxia.Journal of neuroinflammation · 2026Article
- An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.Archives of toxicology · 2025Review
- Emerging Nanotechnology for the Treatment of Alzheimer's Disease.CNS & neurological disorders drug targets · 2024Review
- Tissue Factor and Its Cerebrospinal Fluid Protein Profiles in Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- Thrombin-Induced Microglia Activation Modulated through Aryl Hydrocarbon Receptors.International journal of molecular sciences · 2023Article
- Review
- Intracerebral hemorrhage and thrombin-induced alterations in cerebral microvessel matrix.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Review
- Inflammatory Animal Models of Parkinson's Disease.Journal of Parkinson's disease · 2022Review
- Role of Thrombin in Central Nervous System Injury and Disease.Biomolecules · 2021Review
- Short-term treatment with dabigatran alters protein expression patterns in a late-stage tau-based Alzheimer's disease mouse model.Biochemistry and biophysics reports · 2020Article
- Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer's Disease.Frontiers in neuroscience · 2020Review
- Anti-inflammatory Activity of Ursolic Acid in MPTP-Induced Parkinsonian Mouse Model.Neurotoxicity research · 2019Article
- Delayed Treatment of Capsaicin Produces Partial Motor Recovery by Enhancing Dopamine Function in MPPExperimental neurobiology · 2019Article
- Inhibition of Microglia-Derived Oxidative Stress by Ciliary Neurotrophic Factor Protects Dopamine Neurons In Vivo from MPP⁺ Neurotoxicity.International journal of molecular sciences · 2018Article
- Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches.European journal of pharmacology · 2018Review
- Acetyl-L-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats.Molecular neurobiology · 2018Article
- Capsaicin Protects Against Oxidative Insults and Alleviates Behavioral Deficits in Rats with 6-OHDA-Induced Parkinson's Disease via Activation of TRPV1.Neurochemical research · 2017Article
- P2YJournal of pain research · 2017Article
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study examined whether thrombin-induced microglial activation could contribute to death of dopaminergic neurons in the rat substantia nigra (SN) in vivo. Seven days after thrombin injection into the SN, tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral dopaminergic neurons. In parallel, thrombin-activated microglia, visualized by immunohistochemical staining using antibodies against the complement receptor type 3 (OX-42) and the major histocompatibility complex class II antigens were also observed in the SN, where degeneration of nigral neurons was found. Reverse transcription PCR at various time points demonstrated that activated microglia in vivo exhibited an early and transient expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and several proinflammatory cytokines, including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor alpha. Western blot analysis and double-label immunohistochemistry showed an increase in the expression of iNOS and COX-2 and the colocalization of these proteins within microglia. The thrombin-induced loss of SN dopaminergic neurons was partially inhibited by NG-nitro-L-arginine methyl ester hydrochloride, an NOS inhibitor, and by DuP-697, a COX-2 inhibitor. Additional studies demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) were activated in the SN as early as 30 min after thrombin injection, and that these kinases were localized within microglia. Inhibition of ERK1/2 and p38 MAPK reduced iNOS and COX-2 mRNA expression and rescued dopaminergic neurons in the SN. The present results strongly suggest that microglial activation triggered by endogenous compound(s) such as thrombin may be involved in the neuropathological processes of dopaminergic neuronal cell death that occur in Parkinson's disease.
Indexed as
Identifiers
12843292PMC6741241W1576211545What OpenQuestion holds
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.