ArticleInternational journal of molecular sciences2014
Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189.
Article in International journal of molecular sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- Mild and repetitive mild traumatic brain injury: Changes in microglial cells and synapses.Neural regeneration research · 2026Article
- Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies.Cells · 2026Review
- Mild Traumatic Brain Injury Impairs Fear Extinction and Network Excitability in the Infralimbic Cortex.Journal of neurotrauma · 2025Article
- Cannabinoid Receptor 2 (CB2) in Macrophages: A Promising Clinical Target for Immune Disorders.International journal of molecular sciences · 2025Review
- Oral Supplementation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Can Prevent TBI-Induced Visual, Motor, and Emotional Deficits in Mice.Molecular neurobiology · 2025Article
- Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025Review
- Modulation of cannabinoid receptor 2 alters neuroinflammation and reduces formation of alpha-synuclein aggregates in a rat model of nigral synucleinopathy.Journal of neuroinflammation · 2024Article
- Sphingolipid changes in mouse brain and plasma after mild traumatic brain injury at the acute phases.Lipids in health and disease · 2024Article
- Flipping the GPCR Switch: Structure-Based Development of Selective Cannabinoid Receptor 2 Inverse Agonists.ACS central science · 2024Article
- An Open-Source Mouse Chronic EEG Array System with High-Density MXene-Based Skull Surface Electrodes.eNeuro · 2024Article
- Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries.Experimental neurology · 2024Article
- Alzheimer's Disease and Cancer: Common Targets.Mini reviews in medicinal chemistry · 2024Review
- Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.Biomedicines · 2023Review
- Immunomodulatory Actions of Cannabinoids: Clinical Correlates and Therapeutic Opportunities for Allergic Inflammation.The journal of allergy and clinical immunology. In practice · 2023Review
- Article
- Cannabinoid CB2 Receptors in Neurodegenerative Proteinopathies: New Insights and Therapeutic Potential.Biomedicines · 2022Review
- A Long-Term Safety and Efficacy Report on Intravitreal Delivery of Adipose Stem Cells and Secretome on Visual Deficits After Traumatic Brain Injury.Translational vision science & technology · 2022Article
- Raloxifene Mitigates Emotional Deficits after Mild Traumatic Brain Injury in Mice.Neurotrauma reports · 2022Article
- The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models.International journal of molecular sciences · 2021Review
- Dependence of visual and cognitive outcomes on animal holder configuration in a rodent model of blast overpressure exposure.Vision research · 2021Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
We have developed a focal blast model of closed-head mild traumatic brain injury (TBI) in mice. As true for individuals that have experienced mild TBI, mice subjected to 50-60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2), we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50-60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.
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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.