Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids
(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the <i>Cannabis Sativa</i> and <i>Indica</i> plants. However, their role in mechanisms leading to neurodegeneration following...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9773 |
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| author | Elisa Landucci Costanza Mazzantini Daniele Lana Pier Luigi Davolio Maria Grazia Giovannini Domenico E. Pellegrini-Giampietro |
| author_facet | Elisa Landucci Costanza Mazzantini Daniele Lana Pier Luigi Davolio Maria Grazia Giovannini Domenico E. Pellegrini-Giampietro |
| author_sort | Elisa Landucci |
| collection | DOAJ |
| description | (1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the <i>Cannabis Sativa</i> and <i>Indica</i> plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of <i>Cannabis</i> extracts (Bedrocan, FM2) or selected cannabinoids (Δ<sup>9</sup>-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ<sup>9</sup>-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death. |
| first_indexed | 2024-03-10T07:35:55Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:55Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9784453410674435a8bb2fa468935e852023-11-22T13:27:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218977310.3390/ijms22189773Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected CannabinoidsElisa Landucci0Costanza Mazzantini1Daniele Lana2Pier Luigi Davolio3Maria Grazia Giovannini4Domenico E. Pellegrini-Giampietro5Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyFarmacia del Madonnone, Via Aretina 9R, 50135 Florence, ItalyDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the <i>Cannabis Sativa</i> and <i>Indica</i> plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of <i>Cannabis</i> extracts (Bedrocan, FM2) or selected cannabinoids (Δ<sup>9</sup>-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ<sup>9</sup>-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death.https://www.mdpi.com/1422-0067/22/18/9773Bedrocan extractFM2 extractcerebral ischemianeuroprotectionCB1CB2 |
| spellingShingle | Elisa Landucci Costanza Mazzantini Daniele Lana Pier Luigi Davolio Maria Grazia Giovannini Domenico E. Pellegrini-Giampietro Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids International Journal of Molecular Sciences Bedrocan extract FM2 extract cerebral ischemia neuroprotection CB1 CB2 |
| title | Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids |
| title_full | Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids |
| title_fullStr | Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids |
| title_full_unstemmed | Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids |
| title_short | Neuroprotective Effects of Cannabidiol but Not Δ<sup>9</sup>-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with <i>Cannabis</i> Extracts and Selected Cannabinoids |
| title_sort | neuroprotective effects of cannabidiol but not δ sup 9 sup tetrahydrocannabinol in rat hippocampal slices exposed to oxygen glucose deprivation studies with i cannabis i extracts and selected cannabinoids |
| topic | Bedrocan extract FM2 extract cerebral ischemia neuroprotection CB1 CB2 |
| url | https://www.mdpi.com/1422-0067/22/18/9773 |
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