Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis

Pan, Steven D.; Grandgirard, Denis; Leib, Stephen L.

doi:10.3389/fcimb.2020.588195

Cited by 11 publications

(8 citation statements)

References 89 publications

(121 reference statements)

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“…On the other hand, Pan et al observed a shift of microglia towards an anti-inflammatory phenotype in the hippocampus and cortex by administering the agonist JWH-133 in a pneumococcal meningitis paradigm [ 111 ]. In animal models of alcoholism, the administration of the CB 2 r agonist AM1241 promoted liver regeneration in a thioacetamide (TAA)-induced liver injury model by suppressing TLR4/miR-155/NF-κB p65 pathway [ 112 ].…”

Section: Resultsmentioning

confidence: 99%

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

García-Gutiérrez

Navarrete

Gasparyan

et al. 2022

IJMS

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Cumulative evidence has pointed out cannabinoid CB2 receptors (CB2r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB2r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles. The search strategy was as follows: “Receptor, Cannabinoid, CB2” AND “Alcohol-Related Disorders” AND “human/or patients”; “Receptor, Cannabinoid, CB2” AND “Alcohol” OR “Ethanol” AND “rodents/or mice/or rats”. Pharmacological approaches demonstrated that the activation or blockade of CB2r modulated different alcohol-addictive behaviors. Rodent models of alcoholism revealed significant alterations of CB2r in brain areas of the reward system. In addition, mice lacking CB2r (CB2KO) show increased alcohol consumption, motivation, and relapse alterations. It has been stressed that the potential neurobiological mechanisms underlying their behavioral effects involve critical elements of the alcohol reward system. Interestingly, recent postmortem studies showed CB2r gene expression alterations in brain areas of alcoholic patients. Moreover, although the number of studies is limited, the results revealed an association between some genetic alterations of the CB2r gene and an increased risk for developing AUD. This review provides evidence that CB2r may play a role in alcohol addiction. Clinical studies are necessary to figure out whether CB2r ligands may prove useful for the treatment of AUD in humans.

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Section: Resultsmentioning

confidence: 99%

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

García-Gutiérrez

Navarrete

Gasparyan

et al. 2022

IJMS

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“…The specific deletion of Cannabinoid Receptor 2 (CB2) receptors in microglia and dopamine neurons has been shown to induce neuroinflammation, alter locomotor activity, and induce behavioral changes via alcohol [60]. JWH-133 (dimethylbutyl-deoxy-delta-8-THC), a selective agonist of CB2, has been shown to reduce the cytokine levels, such as CINC-1, -2α/β, and MIP-3α, in parenchymal cells and change microglia towards the non-inflammatory phenotype; however, it could not reverse or ameliorate brain damage [61]. Microglia express several receptors depending on the proinflammatory or anti-inflammatory environment prevailing within the vicinity.…”

Section: Expressions and Activation Of Receptors In Microgliamentioning

confidence: 99%

Alcohol and the Brain–Gut Axis: The Involvement of Microglia and Enteric Glia in the Process of Neuro-Enteric Inflammation

Khan,

Chang

2023

Cells

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Binge or chronic alcohol consumption causes neuroinflammation and leads to alcohol use disorder (AUD). AUD not only affects the central nervous system (CNS) but also leads to pathologies in the peripheral and enteric nervous systems (ENS). Thus, understanding the mechanism of the immune signaling to target the effector molecules in the signaling pathway is necessary to alleviate AUD. Growing evidence shows that excessive alcohol consumption can activate neuroimmune cells, including microglia, and change the status of neurotransmitters, affecting the neuroimmune system. Microglia, like peripheral macrophages, are an integral part of the immune defense and represent the reticuloendothelial system in the CNS. Microglia constantly survey the CNS to scavenge the neuronal debris. These cells also protect parenchymal cells in the brain and spinal cord by repairing nerve circuits to keep the nervous system healthy against infectious and stress-derived agents. In an activated state, they become highly dynamic and mobile and can modulate the levels of neurotransmitters in the CNS. In several ways, microglia, enteric glial cells, and macrophages are similar in terms of causing inflammation. Microglia also express most of the receptors that are constitutively present in macrophages. Several receptors on microglia respond to the inflammatory signals that arise from danger-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), endotoxins (e.g., lipopolysaccharides), and stress-causing molecules (e.g., alcohol). Therefore, this review article presents the latest findings, describing the roles of microglia and enteric glial cells in the brain and gut, respectively, and their association with neurotransmitters, neurotrophic factors, and receptors under the influence of binge and chronic alcohol use, and AUD.

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“…Staining and categorical analysis of microglia morphology. Brains collected at 42 hpi were sampled into 45 µm free-floating cryosections and stained with Iba-1 for microglia as previously described 58 . Images of microglia in the cortex were randomly sampled under × 400 magnification from each animal (three sections per animal).…”

Section: Histomorphometric Analysis Of Cortical Damage and Hippocampa...mentioning

confidence: 99%

“…Images of microglia in the cortex were randomly sampled under × 400 magnification from each animal (three sections per animal). Cells were classified into three categories, as previously described 58 : resting = round, oval body with thin and long processes; intermediate/hypertrophied = enlarged, darkened cell body with thick processes and less branching; reactive = enlarged, darkened cell body with little or no processes. The percentage of the different categories was calculated by first counting the total microglial cell number in the image followed by counting the three states of the microglia.…”

Section: Histomorphometric Analysis Of Cortical Damage and Hippocampa...mentioning

confidence: 99%

The CCR5 antagonist maraviroc exerts limited neuroprotection without improving neurofunctional outcome in experimental pneumococcal meningitis

Steinfort

Grandgirard

et al. 2022

Sci Rep

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One-third of pneumococcal meningitis (PM) survivors suffer from neurological sequelae including learning disabilities and hearing loss due to excessive neuroinflammation. There is a lack of efficacious compounds for adjuvant therapy to control this long-term consequence of PM. One hallmark is the recruitment of leukocytes to the brain to combat the bacterial spread. However, this process induces excessive inflammation, causing neuronal injury. Maraviroc (MVC)—a CCR5 antagonist—was demonstrated to inhibit leukocyte recruitment and attenuate neuroinflammation in several inflammatory diseases. Here, we show that in vitro, MVC decreased nitric oxide production in astroglial cells upon pneumococcal stimulation. In vivo, infant Wistar rats were infected with 1 × 104 CFU/ml S. pneumoniae and randomized for treatment with ceftriaxone plus MVC (100 mg/kg) or ceftriaxone monotherapy. During the acute phase, neuroinflammation in the CSF was measured and histopathological analyses were performed to determine neuronal injury. Long-term neurofunctional outcome (learning/memory and hearing capacity) after PM was assessed. MVC treatment reduced hippocampal cell apoptosis but did not affect CSF neuroinflammation and the neurofunctional outcome after PM. We conclude that MVC treatment only exerted limited effect on the pathophysiology of PM and is, therefore, not sufficiently beneficial in this experimental paradigm of PM.

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Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis

Cited by 11 publications

References 89 publications

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Alcohol and the Brain–Gut Axis: The Involvement of Microglia and Enteric Glia in the Process of Neuro-Enteric Inflammation

The CCR5 antagonist maraviroc exerts limited neuroprotection without improving neurofunctional outcome in experimental pneumococcal meningitis

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