ArticleBrain research2012
NAAG peptidase inhibitor reduces cellular damage in a model of TBI with secondary hypoxia.
Article in Brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 33 citations in OpenAlex.
- Mass spectrometry-guided discovery of novel GCPII inhibitor scaffolds.Frontiers in pharmacology · 2025Article
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Temperature induces brain-intake shift of recombinant high-density lipoprotein after traumatic brain injury.Journal of nanobiotechnology · 2024Article
- Neuropharmacological insight into preventive intervention in posttraumatic epilepsy based on regulating glutamate homeostasis.CNS neuroscience & therapeutics · 2023Review
- Dendrimer-enabled targeted delivery attenuates glutamate excitotoxicity and improves motor function in a rabbit model of cerebral palsy.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Novel image analysis tool for rapid screening of cell morphology in preclinical animal models of disease.Heliyon · 2023Article
- Review
- Enhanced Oral Bioavailability of 2-(Phosphonomethyl)-pentanedioic Acid (2-PMPA) from its (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl (ODOL)-Based Prodrugs.Molecular pharmaceutics · 2019Article
- Mitochondrial uncoupling prodrug improves tissue sparing, cognitive outcome, and mitochondrial bioenergetics after traumatic brain injury in male mice.Journal of neuroscience research · 2018Article
- Enhanced Brain Delivery of 2-(Phosphonomethyl)pentanedioic Acid Following Intranasal Administration of Its γ-Substituted Ester Prodrugs.Molecular pharmaceutics · 2017Article
- Traumatic brain injury using mouse models.Translational stroke research · 2014Review
- Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II.Bioorganic & medicinal chemistry letters · 2014Article
- The prostate-specific membrane antigen: lessons and current clinical implications from 20 years of research.Urologic oncology · 2014Review
- HIF-1α involves in neuronal apoptosis after traumatic brain injury in adult rats.Journal of molecular neuroscience : MN · 2013Article
- NAAG peptidase inhibitor improves motor function and reduces cognitive dysfunction in a model of TBI with secondary hypoxia.Brain research · 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
7 authors at 3 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) leads to a rapid and excessive glutamate elevation in the extracellular milieu, resulting in neuronal degeneration and astrocyte damage. Posttraumatic hypoxia is a clinically relevant secondary insult that increases the magnitude and duration of glutamate release following TBI. N-acetyl-aspartyl glutamate (NAAG), a prevalent neuropeptide in the CNS, suppresses presynaptic glutamate release by its action at the mGluR3 (a group II metabotropic glutamate receptor). However, extracellular NAAG is rapidly converted into NAA and glutamate by the catalytic enzyme glutamate carboxypeptidase II (GCPII) reducing presynaptic inhibition. We previously reported that the GCPII inhibitor ZJ-43 and its prodrug di-ester PGI-02776 reduce the deleterious effects of excessive extracellular glutamate when injected systemically within the first 30 min following injury. We now report that PGI-02776 (10mg/kg) is neuroprotective when administered 30 min post-injury in a model of TBI plus 30 min of hypoxia (FiO(2)=11%). 24h following TBI with hypoxia, significant increases in neuronal cell death in the CA1, CA2/3, CA3c, hilus and dentate gyrus were observed in the ipsilateral hippocampus. Additionally, there was a significant reduction in the number of astrocytes in the ipsilateral CA1, CA2/3 and in the CA3c/hilus/dentate gyrus. Administration of PGI-02776 immediately following the cessation of hypoxia significantly reduced neuronal and astrocytic cell death across all regions of the hippocampus. These findings indicate that NAAG peptidase inhibitors administered post-injury can significantly reduce the deleterious effects of TBI combined with a secondary hypoxic insult.
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.