title: Endocannabinoids reduce cerebral damage after hypoxic-ischemic injury in perinatal rats.
abstract: Hypoxic-ischemic (HI) insult during the perinatal period remains as one of the most common causes of brain injury and produces long-term neurological deficits, and there is a growing need for effective therapies. The aim of the present work was to perform a prospective study designed to assess the possible protector effect of two endocannabinoids: 2-arachidonoylglycerol (2AG) and anandamide (AEA) in the brain after HI injury in perinatal rat model. We evaluate their effects on cell death and check several cellular parameters. 7-days-old Wistar rats were assigned to four different experimental groups (n=7-10): Sham, HI, and HI treated with 2AG or AEA. The injury was induced by the left carotid artery ligature and subsequent exposure to 8% O(2) for 120 min. Immediately after the injury, treated groups received a single dose of 2AG (1mg/kg) or AEA (5mg/kg) and then animals were sacrificed 24, 72 h or 7 days after the HI event. Brains fixed by perfusion were stained with Nissl for morphological studies, and non-fixed brains were dissociated and analyzed by flow cytometry to quantify apoptosis, mitochondrial state, intracellular calcium and reactive oxygen species. Our results show that both 2AG and AEA have beneficial effects after HI injury in this rat model, producing a remarkable amelioration of brain injury, reducing apoptotic cell death, contributing to the maintenance of mitochondrial functionality, and improving cellular parameters such as the influx of calcium and ROS production.
authors: Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country, E-48940 Leioa, Vizcaya, Spain. idoia.lara.celador@gmail.com
authors: Idoia
authors: I
authors: Lara-Celador
authors: Lourdes
authors: L
authors: Castro-Ortega
authors: Antonia
authors: A
authors: Alvarez
authors: Felipe
authors: F
authors: Goñi-de-Cerio
authors: Jaione
authors: J
authors: Lacalle
authors: Enrique
authors: E
authors: Hilario
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001095:Arachidonic Acids / Q000494:pharmacology*; D063388:Endocannabinoids / Q000494:pharmacology*; D005434:Flow Cytometry; D005989:Glycerides / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; C094503:glyceryl 2-arachidonate; C078814:anandamide