ArticleJournal of neurotrauma2013
Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury.
Article in Journal of neurotrauma, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 122 citations in OpenAlex.
- Mechanisms of inflammatory response in secondary brain injury: a review of computational approaches, challenges, and future directions.Biomechanics and modeling in mechanobiology · 2026Review
- Integrated multi-omic profiling uncovers endocannabinoid system as a driver of nerve agent-induced cognitive dysfunction in guinea pigs.Archives of toxicology · 2025Article
- ABHD8 antagonizes inflammation by facilitating chaperone-mediated autophagy-mediated degradation of NLRP3.Autophagy · 2025Article
- Inhibition of diacylglycerol lipase α induced blood-brain barrier breach in female Sprague-Dawley rats.The Journal of physiology · 2025Article
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.The Journal of pharmacology and experimental therapeutics · 2024Review
- Overexpression of endothelial S1pr2 promotes blood-brain barrier disruption via JNK/c-Jun/MMP-9 pathway after traumatic brain injury in bothFrontiers in pharmacology · 2024Article
- The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.Psychological medicine · 2023Review
- Repeated Mild Traumatic Brain Injury and JZL184 Produce Sex-Specific Increases in Anxiety-Like Behavior and Alcohol Consumption in Wistar Rats.Journal of neurotrauma · 2023Article
- Investigating the Effects of Exogenous and Endogenous 2-Arachidonoylglycerol on Retinal CB1 Cannabinoid Receptors and Reactive Microglia in Naive and Diseased Retina.International journal of molecular sciences · 2023Article
- Article
- JZL184 increases anxiety-like behavior and does not reduce alcohol consumption in female rats after repeated mild traumatic brain injury.bioRxiv : the preprint server for biology · 2023Article
- The serine hydrolase ABHD6 controls survival and thermally induced seizures in a mouse model of Dravet syndrome.Neurobiology of disease · 2023Article
- Cannabinoids in traumatic brain injury and related neuropathologies: preclinical and clinical research on endogenous, plant-derived, and synthetic compounds.Journal of neuroinflammation · 2023Review
- Article
- Hippocampal vulnerability to hyperhomocysteinemia worsens pathological outcomes of mild traumatic brain injury in rats.Journal of central nervous system disease · 2023Article
- Review
- Review
- Administration of ΔCannabis and cannabinoid research · 2022Article
- Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside.Pharmaceutics · 2022Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
2-arachidonylglycerol (2-AG) is the most abundant endocannabinoid in the central nervous system and is elevated after brain injury. Because of its rapid hydrolysis, however, the compensatory and neuroprotective effect of 2-AG is short-lived. Although inhibition of monoacylglycerol lipase, a principal enzyme for 2-AG degradation, causes a robust increase of brain levels of 2-AG, it also leads to cannabinoid receptor desensitization and behavioral tolerance. Alpha/beta hydrolase domain 6 (ABHD6) is a novel 2-AG hydrolytic enzyme that accounts for a small portion of 2-AG hydrolysis, but its inhibition is believed to elevate the levels of 2-AG within the therapeutic window without causing side effect. Using a mouse model of traumatic brain injury (TBI), we found that post-insult chronic treatment with a selective ABHD6 inhibitor WWL70 improved motor coordination and working memory performance. WWL70 treatment reduced lesion volume in the cortex and neurodegeneration in the dendate gyrus. It also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. This study indicates that the fine-tuning of 2-AG signaling by modulating ABHD6 activity can exert anti-inflammatory and neuroprotective effects in 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.