ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019
Depression following traumatic brain injury in mice is associated with down-regulation of hippocampal astrocyte glutamate transporters by thrombin.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Effectiveness of Pharmacotherapy for Depression after Adult Traumatic Brain Injury: an Umbrella Review.Neuropsychology review · 2023Pooled it
- Effect of Physical Exercise on Acute Post-traumatic Hyperexcitability: The Role of Thrombin/PAR1 Signaling.Molecular neurobiology · 2026Article
- Brain pericytes upregulate glutamate uptake by astrocytesIBRO neuroscience reports · 2025Article
- Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury.Biomolecules · 2025Article
- Synaptic Pathology in Traumatic Brain Injury and Therapeutic Insights.International journal of molecular sciences · 2025Review
- Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Short-term neural and glial response to mild traumatic brain injury in the hippocampus.Biophysical journal · 2024Article
- Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.Clinical proteomics · 2024Article
- Acute and Chronic Neural and Glial Response to Mild Traumatic Brain Injury in the Hippocampus.bioRxiv : the preprint server for biology · 2024Article
- Electrochemical and biosensor techniques to monitor neurotransmitter changes with depression.Analytical and bioanalytical chemistry · 2024Review
- Article
- Neuropharmacological insight into preventive intervention in posttraumatic epilepsy based on regulating glutamate homeostasis.CNS neuroscience & therapeutics · 2023Review
- Review
- Inhibition of LRRK2 Attenuates Depression-Related Symptoms in Mice with Moderate Traumatic Brain Injury.Cells · 2023Article
- Neuroprotective astroglial response to neural damage and its relevance to affective disorders.Exploration of neuroprotective therapy · 2023Article
- Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases.Neural regeneration research · 2022Review
- Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery.Pharmaceutics · 2022Article
- TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications.Biomedicines · 2022Review
- Glutamate Efflux across the Blood-Brain Barrier: New Perspectives on the Relationship between Depression and the Glutamatergic System.Metabolites · 2022Review
- Physical Exercise as a Modulator of Vascular Pathology and Thrombin Generation to Improve Outcomes After Traumatic Brain Injury.Molecular neurobiology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression after traumatic brain injury (TBI) is common but the mechanisms by which TBI causes depression are unknown. TBI decreases glutamate transporters GLT-1 and GLAST and allows extravasation of thrombin. We examined the effects of thrombin on transporter expression in primary hippocampal astrocytes. Application of a PAR-1 agonist caused down-regulation of GLT-1, which was prevented by inhibition of Rho kinase (ROCK). To confirm these mechanisms in vivo, we subjected mice to closed-skull TBI. Thrombin activity in the hippocampus increased one day following TBI. Seven days following TBI, expression of GLT-1 and GLAST was reduced in the hippocampus, and this was prevented by administration of the PAR-1 antagonist SCH79797. Inhibition of ROCK attenuated the decrease in GLT-1, but not GLAST, after TBI. We measured changes in glutamate levels in the hippocampus seven days after TBI using an implanted biosensor. Stress-induced glutamate levels were significantly increased following TBI and this was attenuated by treatment with the ROCK inhibitor fasudil. We quantified depressive behavior following TBI and found that inhibition of PAR-1 or ROCK decreased these behaviors. These results identify a novel mechanism by which TBI results in down-regulation of astrocyte glutamate transporters and implicate astrocyte and glutamate transporter dysfunction in depression following TBI.
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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.