The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines
Endocannabinoids are involved in neuroprotection through numerous biochemical pathways. We have shown that the endocannabinoid 2-arachidonoyl glycerol (2-AG) is released in mouse brain after closed head injury (CHI), and treatment with exogenous 2-AG exerts neuroprotection via the central cannabinoi...
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| Format: | Article |
| Language: | English |
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Elsevier
2006-05-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105003074 |
| _version_ | 1818862596460118016 |
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| author | David Panikashvili Na'ama A. Shein Raphael Mechoulam Victoria Trembovler Ron Kohen Alexander Alexandrovich Esther Shohami |
| author_facet | David Panikashvili Na'ama A. Shein Raphael Mechoulam Victoria Trembovler Ron Kohen Alexander Alexandrovich Esther Shohami |
| author_sort | David Panikashvili |
| collection | DOAJ |
| description | Endocannabinoids are involved in neuroprotection through numerous biochemical pathways. We have shown that the endocannabinoid 2-arachidonoyl glycerol (2-AG) is released in mouse brain after closed head injury (CHI), and treatment with exogenous 2-AG exerts neuroprotection via the central cannabinoid receptor CB1. This process involves inhibition of inflammatory signals that are mediated by activation of the transcription factor NF-kB. The present study was designed to examine the effect of 2-AG on the blood–brain barrier (BBB) and the possible inhibition of the early expression of proinflammatory cytokines, which are implicated in BBB disruption. We found that 2-AG decreased BBB permeability and inhibited the acute expression of the main proinflammatory cytokines: TNF-α, IL-1β and IL-6. It also augmented the levels of endogenous antioxidants. We suggest that 2-AG exerts neuroprotection in part by inhibition of the early (1–4 h) inflammatory response and augmentation of the brain reducing power. |
| first_indexed | 2024-12-19T10:02:23Z |
| format | Article |
| id | doaj.art-8ff596dcb3a24d998b21525851dcf445 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T10:02:23Z |
| publishDate | 2006-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-8ff596dcb3a24d998b21525851dcf4452022-12-21T20:26:37ZengElsevierNeurobiology of Disease1095-953X2006-05-01222257264The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokinesDavid Panikashvili0Na'ama A. Shein1Raphael Mechoulam2Victoria Trembovler3Ron Kohen4Alexander Alexandrovich5Esther Shohami6Department of Pharmacology, Faculty of Medicine, School of Pharmacy, The Hebrew University School of Jerusalem, Jerusalem 91120, Israel; Medicinal Chemistry and Natural Products, The Hebrew University School of Pharmacy, Faculty of Medicine, Jerusalem, IsraelDepartment of Pharmacology, Faculty of Medicine, School of Pharmacy, The Hebrew University School of Jerusalem, Jerusalem 91120, IsraelMedicinal Chemistry and Natural Products, The Hebrew University School of Pharmacy, Faculty of Medicine, Jerusalem, IsraelDepartment of Pharmacology, Faculty of Medicine, School of Pharmacy, The Hebrew University School of Jerusalem, Jerusalem 91120, IsraelPharmaceutics, The Hebrew University School of Pharmacy, Faculty of Medicine, Jerusalem, IsraelDepartment of Pharmacology, Faculty of Medicine, School of Pharmacy, The Hebrew University School of Jerusalem, Jerusalem 91120, IsraelDepartment of Pharmacology, Faculty of Medicine, School of Pharmacy, The Hebrew University School of Jerusalem, Jerusalem 91120, Israel; Corresponding author. Fax: +972 2 675 8741.Endocannabinoids are involved in neuroprotection through numerous biochemical pathways. We have shown that the endocannabinoid 2-arachidonoyl glycerol (2-AG) is released in mouse brain after closed head injury (CHI), and treatment with exogenous 2-AG exerts neuroprotection via the central cannabinoid receptor CB1. This process involves inhibition of inflammatory signals that are mediated by activation of the transcription factor NF-kB. The present study was designed to examine the effect of 2-AG on the blood–brain barrier (BBB) and the possible inhibition of the early expression of proinflammatory cytokines, which are implicated in BBB disruption. We found that 2-AG decreased BBB permeability and inhibited the acute expression of the main proinflammatory cytokines: TNF-α, IL-1β and IL-6. It also augmented the levels of endogenous antioxidants. We suggest that 2-AG exerts neuroprotection in part by inhibition of the early (1–4 h) inflammatory response and augmentation of the brain reducing power.http://www.sciencedirect.com/science/article/pii/S0969996105003074Traumatic brain injuryEndocannabinoidsNeuroprotectionBBB integrityInflammationCytokines |
| spellingShingle | David Panikashvili Na'ama A. Shein Raphael Mechoulam Victoria Trembovler Ron Kohen Alexander Alexandrovich Esther Shohami The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines Neurobiology of Disease Traumatic brain injury Endocannabinoids Neuroprotection BBB integrity Inflammation Cytokines |
| title | The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines |
| title_full | The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines |
| title_fullStr | The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines |
| title_full_unstemmed | The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines |
| title_short | The endocannabinoid 2-AG protects the blood–brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines |
| title_sort | endocannabinoid 2 ag protects the blood brain barrier after closed head injury and inhibits mrna expression of proinflammatory cytokines |
| topic | Traumatic brain injury Endocannabinoids Neuroprotection BBB integrity Inflammation Cytokines |
| url | http://www.sciencedirect.com/science/article/pii/S0969996105003074 |
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