title: The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats.
abstract: An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults. We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes. Effects of an acute post-insult administration of the endocannabinoid receptor agonist WIN55,212-2 on early seizure occurrence, animal mortality and hippocampal cell loss were studied in the lithium-pilocarpine status model. A single dose of WIN55,212-2 (5mg/kg) administered four hours after the end of status epilepticus (SE) reduced the incidence of early seizures during the first two post-SE days though did not change their duration and latency. Brief 4-6-Hz spike-wave discharges appeared de novo in the latent post-SE period and the acute administration of WIN55,212-2 also reduced the incidence of the epileptiform events. A single dose of WIN55,212-2 administered soon after SE improved survival of animals and reduced cell loss in the dentate hilus but did not prevent appearance of spontaneous recurrent seizures in the chronic period. Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.
authors: Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences, Moscow, Russia.
authors: Elena M
authors: EM
authors: Suleymanova
authors: Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences, Moscow, Russia.
authors: Vitalia A
authors: VA
authors: Shangaraeva
authors: Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors: Clementina M
authors: CM
authors: van Rijn
authors: Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences, Moscow, Russia. Electronic address: lvinogradova@gmail.com.
authors: Lyudmila V
authors: LV
authors: Vinogradova
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D000069280:Electrocorticography; D018020:Lithium Compounds; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010862:Pilocarpine; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013226:Status Epilepticus / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis
chemical_list: D000927:Anticonvulsants; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D018020:Lithium Compounds; D009025:Morpholines; D009281:Naphthalenes; D018696:Neuroprotective Agents; D010862:Pilocarpine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
keywords: endocannabinoid system; epilepsy; mortality; neurodegeneration; spike–wave discharges; status epilepticus