Granulocyte Colony-Stimulating Factor Enhances Brain Repair Following Traumatic Brain Injury Without Requiring Activation of Cannabinoid Receptors
| Autor: | Shijie Song, Cesar V. Borlongan, Juan Sanchez-Ramos, Xiaoyuan Kong, Vasyl Sava |
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| Rok vydání: | 2021 |
| Předmět: |
Agonist
Male Cannabinoid receptor Traumatic brain injury medicine.drug_class Arachidonic Acids Pharmacology Glycerides Receptor Cannabinoid CB2 Downregulation and upregulation Receptor Cannabinoid CB1 Brain Injuries Traumatic Granulocyte Colony-Stimulating Factor Cannabinoid receptor type 2 Medicine Animals Pharmacology (medical) Receptor Receptors Cannabinoid Cannabinoid Receptor Antagonists Original Research Cannabinoid Receptor Agonists biology business.industry Brain medicine.disease Endocannabinoid system Mice Inbred C57BL Disease Models Animal Complementary and alternative medicine nervous system biology.protein lipids (amino acids peptides and proteins) Mitogen-Activated Protein Kinases business Neurotrophin Endocannabinoids Signal Transduction |
| Zdroj: | Cannabis Cannabinoid Res |
| ISSN: | 2578-5125 |
| Popis: | Introduction: Treatment of traumatic brain injury (TBI) with granulocyte colony-stimulating factor (G-CSF) has been shown to enhance brain repair by direct neurotrophic actions on neural cells and by modulating the inflammatory response. Administration of cannabinoids after TBI has also been reported to enhance brain repair by similar mechanisms. Objectives: The primary objective of this study was to test the hypothesis that G-CSF mediates brain repair by interacting with the endocannabinoid system. Methods and Results: (i) Mice that underwent controlled cortical impact (CCI) were treated with G-CSF for 3 days either alone or in the presence of selective cannabinoid receptor 1 (CB1-R) or cannabinoid receptor 2 (CB2-R) agonists and antagonists. The trauma resulted in decreased expression of CB1-R and increased expression of CB2-R in the cortex, striatum, and hippocampus. Cortical and striatal levels of the major endocannabinoid ligand, 2-arachidonoyl-glycerol, were also increased by the CCI. Administration of the hematopoietic cytokine, G-CSF, following TBI, resulted in mitigation or reversal of trauma-induced CB1-R downregulation and CB2-R upregulation in the three brain regions. Treatment with CB1-R agonist (WIN55) or CB2-R agonist (HU308) mimicked the effects of G-CSF. (ii) Pharmacological blockade of CB1-R or CB2-R was not effective in preventing G-CSF's mitigation or reversal of trauma-induced alterations in these receptors. Conclusions: These results suggest that cellular and molecular mechanisms that mediate subacute effects of G-CSF do not depend on activation of CB1 or CB2 receptors. Failure of selective CB receptor antagonists to prevent the effects of G-CSF in this model has to be accepted with caution. CB receptor antagonists can interact with other CB and non-CB receptors. Investigation of the role of CB receptors in this TBI model will require studies with CB1-R and in CB2-R knockout mice to avoid nonspecific interaction of CB receptor agents with other receptors. |
| Databáze: | OpenAIRE |
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