ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2014
Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental traumatic brain injury.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 79 citations in OpenAlex.
- Transcriptomic and histological characteristics of innate immune activation in brain parenchyma in a rat model of neonatal intraventricular hemorrhage.Fluids and barriers of the CNS · 2025Article
- mGluR5 as a Potential Orchestrator of Astrocyte Interactions in Neurological Disorders.Neural plasticity · 2025Review
- Development and validation of a nomogram for predicting mortality in patients with acute severe traumatic brain injury: A retrospective analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- The Physio-Pathological Role of Group I Metabotropic Glutamate Receptors Expressed by Microglia in Health and Disease with a Focus on Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Review
- A multilayer network model of neuron-astrocyte populations in vitro reveals mGluRNetwork neuroscience (Cambridge, Mass.) · 2022Article
- Article
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection.Frontiers in molecular neuroscience · 2022Review
- Unravelling neuroinflammation in abusive head trauma with radiotracer imaging.Pediatric radiology · 2021Review
- Article
- Dopamine and Neuroinflammation in Schizophrenia - Interpreting the Findings from Translocator Protein (18kDa) PET Imaging.Neuropsychiatric disease and treatment · 2021Review
- Enhanced Akt/GSK-3β/CREB signaling mediates the anti-inflammatory actions of mGluR5 positive allosteric modulators in microglia and following traumatic brain injury in male mice.Journal of neurochemistry · 2021Article
- The Emergence of Model Systems to Investigate the Link Between Traumatic Brain Injury and Alzheimer's Disease.Frontiers in aging neuroscience · 2021Review
- Putative mGluR4 positive allosteric modulators activate GNeurochemistry international · 2020Article
- Article
- Attenuation of Acute Intracerebral Hemorrhage-Induced Microglial Activation and Neuronal Death Mediated by the Blockade of Metabotropic Glutamate Receptor 5 In Vivo.Neurochemical research · 2020Article
- Microglial Metabolism After Pediatric Traumatic Brain Injury - Overlooked Bystanders or Active Participants?Frontiers in neurology · 2020Review
- Tanshinone IIA Promotes M2 Microglia by ERβ/IL-10 Pathway and Attenuates Neuronal Loss in Mouse TBI Model.Neuropsychiatric disease and treatment · 2020Article
- Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact.Experimental neurology · 2019Article
- The Neutrophil/Lymphocyte Count Ratio Predicts Mortality in Severe Traumatic Brain Injury Patients.Journal of clinical medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) causes microglial activation and related neurotoxicity that contributes to chronic neurodegeneration and loss of neurological function. Selective activation of metabotropic glutamate receptor 5 (mGluR5) by the orthosteric agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), is neuroprotective in experimental models of TBI, and has potent anti-inflammatory effects in vitro. However, the therapeutic potential of CHPG is limited due to its relatively weak potency and brain permeability. Highly potent, selective and brain penetrant mGluR5 positive allosteric modulators (PAMs) have been developed and show promise as therapeutic agents. We evaluated the therapeutic potential of a novel mGluR5 PAM, VU0360172, after controlled cortical impact (CCI) in mice. Vehicle, VU0360172, or VU0360172 plus mGluR5 antagonist (MTEP), were administered systemically to CCI mice at 3 h post-injury; lesion volume, hippocampal neurodegeneration, microglial activation, and functional recovery were assessed through 28 days post-injury. Anti-inflammatory effects of VU0360172 were also examined in vitro using BV2 and primary microglia. VU0360172 treatment significantly reduced the lesion, attenuated hippocampal neurodegeneration, and improved motor function recovery after CCI. Effects were mediated by mGluR5 as co-administration of MTEP blocked the protective effects of VU0360172. VU0360172 significantly reduced CD68 and NOX2 expression in activated microglia in the cortex at 28 days post-injury, and also suppressed pro-inflammatory signaling pathways in BV2 and primary microglia. In addition, VU0360172 treatment shifted the balance between M1/M2 microglial activation states towards an M2 pro-repair phenotype. This study demonstrates that VU0360172 confers neuroprotection after experimental TBI, and suggests that mGluR5 PAMs may be promising therapeutic agents for head 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.