The Synthetic Cannabinoid URB447 Reduces Brain Injury and the Associated White Matter Demyelination after Hypoxia-Ischemia in Neonatal Rats

Autor: Daniel Alonso-Alconada, Andrea Duranti, Daniele Piomelli, Silvia Carloni, Linda Palma, Rita Crinelli, Francisco J. Alvarez, Walter Balduini
Rok vydání: 2020
Předmět:
Agonist
Cannabinoid receptor
Physiology
medicine.drug_class
Cognitive Neuroscience
medicine.medical_treatment
Excitotoxicity
Hypoxia-ischemia
cannabinoids
URB447
SR141716A
white matter demyelination
neuroprotection
Pharmacology
medicine.disease_cause
Biochemistry
Neuroprotection
Receptor
Cannabinoid
CB2
03 medical and health sciences
cannabinoids
Medicinal and Biomolecular Chemistry
0302 clinical medicine
Receptor
Cannabinoid
CB1
Ischemia
Benzyl Compounds
medicine
Animals
Pyrroles
Hypoxia
Hypoxia-ischemia
URB447
030304 developmental biology
0303 health sciences
business.industry
Cannabinoids
Glutamate receptor
Cell Biology
General Medicine
white matter demyelination
medicine.disease
Endocannabinoid system
White Matter
Astrogliosis
Rats
Animals
Newborn
Brain Injuries
SR141716A
lipids (amino acids
peptides
and proteins)
neuroprotection
Cannabinoid
business
030217 neurology & neurosurgery
Demyelinating Diseases
Research Article
Zdroj: ACS chemical neuroscience, vol 11, iss 9
ACS Chemical Neuroscience
Popis: The number of functions controlled by the endocannabinoid system in health and disease continues growing over the years. In the brain, these include the modulation of harmful events such as glutamate excitotoxicity, oxidative stress, and inflammation, mainly regulated by activation/blockade of CB1/CB2 cannabinoid receptors. In the present work, we evaluated the capacity of the CB1 antagonist/CB2 agonist synthetic cannabinoid URB447 on reducing neurodegeneration after brain injury. By using a model of hypoxia-ischemia (HI) in neonatal rats, we found that URB447 strongly reduced brain injury when administered before HI. A comparable effect was observed with the CB1 antagonist SR141716A, whereas the CB1 agonist WIN-55,212-2 reduced the effect of URB447. When administered 3 h after HI, which is considered a clinically feasible therapeutic window to treat perinatal brain injury in humans, URB447 reduced neurodegeneration and white matter damage. Markers of astrogliosis and microglial activation also appeared reduced. These results confirm the important role played by the endocannabinoid system in the neurodegenerative process and strongly encourage further research into the mechanisms of URB447-induced neuroprotection.
Databáze: OpenAIRE
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