Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion

Autor: Sara Lisai, Elisabetta Murru, Gianfranca Carta, Tiziana Melis, Sebastiano Banni, Laura Muredda, Marina Quartu, Maria Pina Serra, Marianna Boi, Laura Poddighe, Maria Collu
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Cannabinoid receptor
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
medicine.disease_cause
Brain Ischemia
Brain ischemia
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Lipoperoxides
Anandamide
Cerebral cortex
Endocannabinoid system
Temporal Lobe
Frontal Lobe
Ethanolamines
Reperfusion Injury
lipids (amino acids
peptides
and proteins)
Occipital Lobe
medicine.symptom
medicine.medical_specialty
Lipid Peroxides
Docosahexaenoic Acids
Carotid Artery
Common
Polyunsaturated Alkamides
Inflammation
Arachidonic Acids
Palmitic Acids
Glycerides
03 medical and health sciences
Internal medicine
medicine
Animals
PPAR alpha
Rats
Wistar
Bilateral common carotid artery occlusion
Biochemistry
medical
Palmitoylethanolamide
business.industry
Research
Biochemistry (medical)
COX-2
medicine.disease
Amides
Rats
Cerebrovascular Disorders
Oxidative Stress
030104 developmental biology
chemistry
Gene Expression Regulation
Cyclooxygenase 2
Reperfusion
Lipid Peroxidation
business
Reperfusion injury
030217 neurology & neurosurgery
Oxidative stress
Endocannabinoids
Zdroj: Lipids in Health and Disease
ISSN: 1476-511X
Popis: Background The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Methods Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student’s t-test was used to evaluate statistical differences between groups. Results The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. Conclusions The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge.
Databáze: OpenAIRE
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