ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Combination of thrombin and matrix metalloproteinase-9 exacerbates neurotoxicity in cell culture and intracerebral hemorrhage in mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Pathological mechanisms and future therapeutic directions of thrombin in intracerebral hemorrhage: a systematic review.Frontiers in pharmacology · 2024Pooled it
- Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.Biomolecules · 2026Review
- Matrix metalloproteinase‑9 in hemorrhagic transformation after acute ischemic stroke (Review).Molecular medicine reports · 2025Review
- Crosstalk Between Matrix Metalloproteinases and Their Inducer EMMPRIN/CD147: a Promising Therapeutic Target for Intracerebral Hemorrhage.Translational stroke research · 2025Review
- The role of MMPs in intracerebral hemorrhage.Frontiers in cell and developmental biology · 2025Review
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- Opposing MMP-9 Expression in Mesenchymal Stromal Cells and Head and Neck Tumor Cells after Direct 2D and 3D Co-Culture.International journal of molecular sciences · 2023Article
- Anthrax Meningoencephalitis and Intracranial Hemorrhage.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Review
- CM-352 Efficacy in a Mouse Model of Anticoagulant-Associated Intracranial Hemorrhage.Thrombosis and haemostasis · 2022Article
- EMMPRIN Promotes the Expression of MMP-9 and Exacerbates Neurological Dysfunction in a Mouse Model of Intracerebral Hemorrhage.Neurochemical research · 2022Article
- Neuroprotection by Ozanimod Following Intracerebral Hemorrhage in Mice.Frontiers in molecular neuroscience · 2022Article
- Revisiting Minocycline in Intracerebral Hemorrhage: Mechanisms and Clinical Translation.Frontiers in immunology · 2022Review
- Acute Inflammation in Cerebrovascular Disease: A Critical Reappraisal with Focus on Human Studies.Life (Basel, Switzerland) · 2021Review
- Central Nervous System Tissue Regeneration after Intracerebral Hemorrhage: The Next Frontier.Cells · 2021Review
- Ergosta-7,9(11),22-trien-3β-ol Alleviates Intracerebral Hemorrhage-Induced Brain Injury and BV-2 Microglial Activation.Molecules (Basel, Switzerland) · 2021Article
- When the Blood Hits Your Brain: The Neurotoxicity of Extravasated Blood.International journal of molecular sciences · 2021Review
- Role of Thrombin in Central Nervous System Injury and Disease.Biomolecules · 2021Review
- Microglia: A Double-Edged Sword in Intracerebral Hemorrhage From Basic Mechanisms to Clinical Research.Frontiers in immunology · 2021Review
- Expressions and relationship of Krüppel-like factor 15 and endothelial nitric oxide synthase in experimental deep venous thrombosis.Annals of translational medicine · 2020Article
- Matrix Metalloproteinases in Acute Intracerebral Hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The rapid loss of neurons is a major pathological outcome of intracerebral hemorrhage (ICH). Several mechanisms may produce the neurotoxicity observed in ICH, and these include proteolytic enzymes such as thrombin and matrix metalloproteinase-9 (MMP-9). We tested the hypothesis that thrombin and MMP-9 combine to injure neurons in culture and that they interact to promote the acute neurotoxicity that occurs in ICH in vivo. We report that human fetal neurons die when exposed to thrombin or MMP-9 in isolation and that a combination of these two enzymes increased neurotoxicity. The toxicity of thrombin involved protease-activated receptor-1 and the conversion of proMMP-9 to active MMP-9. In ICH, which was induced in mice by the intracerebral injection of autologous blood, significant areas of brain damage, neuronal death, microglia/macrophage activation, and neutrophil accumulation occurred by 24 h of injury. Importantly, these neuropathological features were reduced in MMP-9 null mice compared with wild-type controls, and the concordant antagonism of thrombin using hirudin also alleviated the injury found in MMP-9 null mice. Our collective results demonstrate that thrombin and MMP-9 collaborate to promote neuronal death in culture and in ICH. To improve the prognosis of ICH, the neurotoxic actions of thrombin and MMP-9 must be inhibited early and simultaneously after injury.
Indexed as
Identifiers
What 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.