title: Differential neuroprotection by A(1) receptor activation and A(2A) receptor inhibition following pilocarpine-induced status epilepticus.
abstract: Aiming at a better understanding of the role of A(2A) in temporal lobe epilepsy (TLE), we characterized the effects of the A(2A) antagonist SCH58261 (7-(2-phenylethyl)-5-amino-2(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) on seizures and neuroprotection in the pilocarpine model. The effects of SCH58261 were further analyzed in combination with the A(1) agonist R-Pia (R(-)-N(6)-(2)-phenylisopropyl adenosine). Eight groups were studied: pilocarpine (Pilo), SCH+Pilo, R-Pia+Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, and R-Pia+SCH+Saline. The administration of SCH58261, R-Pia, and R-Pia+SCH58261 prior to pilocarpine increased the latency to SE, and decreased either the incidence of or rate of mortality from SE compared with controls. Administration of R-Pia and R-Pia+SCH58261 prior to pilocarpine reduced the number of Fluoro-Jade B-stained cells in the hippocampus and piriform cortex when compared with control. This study showed that pretreatment with R-Pia and SCH58261 reduces seizure occurrence, although only R-Pia has neuroprotective properties. Further studies are needed to clarify the neuroprotective role of A(2A) in TLE.
authors.affiliation: Departamento de Neurologia e Neurocirurgia, Neurologia Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Fernanda Elisa
authors.initials: FE
authors.lastname: Rosim
authors.forename: Daniele Suzete
authors.initials: DS
authors.lastname: Persike
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
authors.forename: Rebeca Padrão
authors.initials: RP
authors.lastname: Amorim
authors.forename: Daniela Mara
authors.initials: DM
authors.lastname: de Oliveira
authors.forename: Maria José da Silva
authors.initials: MJ
authors.lastname: Fernandes
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D004347:Drug Interactions; D005452:Fluoresceins; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009930:Organic Chemicals / Q000378:metabolism; D010660:Phenylisopropyladenosine / Q000494:pharmacology / Q000627:therapeutic use; D010862:Pilocarpine / Q000633:toxicity; D011743:Pyrimidines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014230:Triazoles / Q000627:therapeutic use
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D005452:Fluoresceins; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D011743:Pyrimidines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C435731:fluoro jade; D010862:Pilocarpine; D010660:Phenylisopropyladenosine; D000241:Adenosine