Immune control by endocannabinoids — New mechanisms of neuroprotection?

Ullrich, Oliver; Merker, Katrin; Timm, Johanna; Tauber, Svantje

doi:10.1016/j.jneuroim.2006.11.018

Cited by 50 publications

(31 citation statements)

References 122 publications

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“…After brain injury, they elicit neuroprotective effects by targeting different cell types and receptor types. The endocannabinoid 2-AG elicits neuroprotective effects via activation of CB1 receptors, which are mainly located on neurons (Eljaschewitsch et al, 2006;Melis et al, 2006;Panikashvili et al, 2001;Ullrich et al, 2007). The vast majority of studies investigating the role of cannabinoids in inflammation or inflammatory pain demonstrate that 2-AG inhibits the production and release of proinflammatory cytokines and the expression of COX-2 (Comelli et al, 2007;Zhang and Chen, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that microglial cells become highly activated after brain injury. Microglial cells change their morphology from a ramified to an amoeboid form, start to proliferate, produce and secrete cytokines, and migrate to the sites of neuronal injury (Block and Hong, 2005;Hanisch and Kettenmann, 2007;Hanisch et al, 2004;Kettenmann, 2006;M€ oller et al, 2000;Ullrich et al, 2007). On one hand, microglial cells serve beneficial functions for neuronal survival by clearing toxic cellular debris and releasing trophic and anti-inflammatory factors (Kohl et al, 2003;Simard et al, 2006;Streit, 2002).…”

Section: Discussionmentioning

confidence: 99%

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2‐Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal‐cannabidiol‐sensitive receptors on microglial cells

Kreutz

Koch

Böttger

et al. 2008

Glia

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Endocannabinoids like 2-arachidonoylglycerol (2-AG) exert neuroprotective effects after brain injuries. According to current concepts, these neuroprotective effects are due to interactions between 2-AG and cannabinoid (CB)1 receptors on neurons. Moreover, 2-AG modulates migration and proliferation of microglial cells which are rapidly activated after brain lesion. This effect is mediated via CB2- and abnormal-cannabidiol (abn-CBD)-sensitive receptors. In the present study, we investigated whether the abn-CBD-sensitive receptor on microglial cells contributes to 2-AG-mediated neuroprotection in organotypic hippocampal slice cultures (OHSCs) after excitotoxic lesion induced by NMDA (50 microM) application for 4 h. This lesion caused neuronal damage and accumulation of microglial cells within the granule cell layer. To analyze the role of abn-CBD-sensitive receptors for neuroprotection and microglial cell accumulation, two agonists of the abn-CBD-sensitive receptor, abn-CBD or 2-AG, two antagonists, 1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen1-yl]-benzene (O-1918) or cannabidiol (CBD), and the CB1 receptor antagonist AM251, were applied to NMDA-lesioned OHSC. Propidium iodide (PI) labeling was used as a marker of degenerating neurons and isolectin B(4) (IB(4)) as a marker of microglial cells. Application of both, abn-CBD or 2-AG to lesioned OHSC significantly decreased the number of IB(4)(+) microglial cells and PI(+) neurons in the dentate gyrus. In contrast to AM251, application of O-1918 or CBD antagonized these effects. When microglial cells were depleted by preincubation of OHSC with the bisphosphonate clodronate (100 microg/mL) for 5 days before excitotoxic lesion, 2-AG and abn-CBD lost their neuroprotective effects. We therefore propose that the endocannabinoid 2-AG exerts its neuroprotective effects via activation of abn-CBD-sensitive receptors on microglial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

2‐Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal‐cannabidiol‐sensitive receptors on microglial cells

Kreutz

Koch

Böttger

et al. 2008

Glia

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“…Cannabinoids also counteract the vasoconstrictive effect of endothelin-1. These effects have been demonstrated in cell culture and animal models and extensively described in reviews (75,76).…”

Section: Synthetic Cannabinoidsmentioning

confidence: 93%

Pharmacology of Traumatic Brain Injury: Where Is the “Golden Bullet”?

Beauchamp

Mutlak

Smith

et al. 2008

Mol Med

154

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Traumatic brain injury (TBI) represents a major health care problem and a significant socioeconomic challenge worldwide. In the United States alone, approximately 1.5 million patients are affected each year, and the mortality of severe TBI remains as high as 35%-40%. These statistics underline the urgent need for efficient treatment modalities to improve posttraumatic morbidity and mortality. Despite advances in basic and clinical research as well as improved neurological intensive care in recent years, no specific pharmacological therapy for TBI is available that would improve the outcome of these patients. Understanding of the cellular and molecular mechanisms underlying the pathophysiological events after TBI has resulted in the identification of new potential therapeutic targets. Nevertheless, the extrapolation from basic research data to clinical application in TBI patients has invariably failed, and results from prospective clinical trials are disappointing. We review the published prospective clinical trials on pharmacological treatment modalities for TBI patients and outline future promising therapeutic avenues in the field.

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“…Thus, in addition to affecting motor function and inflammatory responses, exogenous cannabinoids may also reduce oxidative stress. As a result, administration of exogenous cannabinoids has been touted as a potential therapeutic target in neurodegenerative diseases [11,12,20,[29][30][31][32][33]. The purpose of this review is to highlight potential mechanisms and evidence for the therapeutic use of exogenous cannabinoids specific to PD.…”

Section: Pathogenesis Of Pd and The Cannabinoid Systemmentioning

confidence: 99%

Therapeutic Potential of Cannabinoids in the Treatment of Neuroinflammation Associated with Parkinsons Disease

Little¹,

Villanueva

Klegeris

2011

MRMC

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The cannabinoid system is represented by two principal receptor subtypes, termed CB1 and CB2, along with several endogenous ligands. In the central nervous system it is involved in several processes. CB1 receptors are mainly expressed by neurons and their activation is primarily implicated in psychotropic and motor effects of cannabinoids. CB2 receptors are expressed by glial cells and are thought to participate in regulation of neuroimmune reactions. This review aims to highlight several reported properties of cannabinoids that could be used to inhibit the adverse neuroinflammatory processes contributing to Parkinson's disease and possibly other neurodegenerative disorders. These include anti-oxidant properties of phytocannabinoids and synthetic cannabinoids as well as hypothermic and antipyretic effects. However, cannabinoids may also trigger signaling cascades leading to impaired mitochondrial enzyme activity, reduced mitochondrial biogenesis, and increased oxidative stress, all of which could contribute to neurotoxicity. Therefore, further pharmacological studies are needed to allow rational design of new cannabinoid-based drugs lacking detrimental in vivo effects.

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Immune control by endocannabinoids — New mechanisms of neuroprotection?

Cited by 50 publications

References 122 publications

2‐Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal‐cannabidiol‐sensitive receptors on microglial cells

2‐Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal‐cannabidiol‐sensitive receptors on microglial cells

Pharmacology of Traumatic Brain Injury: Where Is the “Golden Bullet”?

Therapeutic Potential of Cannabinoids in the Treatment of Neuroinflammation Associated with Parkinsons Disease

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