title: A selective adenosine A2A receptor antagonist ameliorated hyperlocomotion in an animal model of lateral fluid percussion brain injury.
abstract: Increased concentration of extracellular adenosine after brain injury is supposed to be one of the causes of secondary brain damage. The purpose of the present study is to examine whether or not administration of adenosine A2A receptor antagonist may be efficacious in ameliorating neurological symptoms by blocking secondary brain damage through cascades initiated by adenosine A2a receptor.Mongolian gerbils were divided into four groups: the trauma-medication (T-M), trauma-saline (T-S), sham-medication (S-M), and sham-saline (S-S) groups. Trauma groups received lateral fluid percussion injury. Medication groups received i.p. injection of SCH58261 (selective adenosine A2A receptor antagonist) until the fifth post-injury day. Open-field locomotion test and grabbing test were conducted before and 1, 3, 5, 7, and 9 days after injury.The total distance of movement in the T-S group was significantly greater than in the other three groups at all time points. In the T-M group, administration of SCH58261 significantly blocked hyperlocomotion, which was observed in the T-S group. There was no significant difference in the total distance among the T-M, S-M, and S-S groups. In the grabbing test, grabbing time was significantly increased in the T-S group 3, 5, 7, and 9 days after the operation. SCH58261 also improved grabbing time in the T-M group.Adenosine A2A antagonist successfully suppressed the trauma-induced hyperlocomotion, presumably by blocking secondary brain damage.
authors.affiliation: Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Saad Habib-E-Rasul
authors.initials: SH
authors.lastname: Mullah
authors.forename: Motoki
authors.initials: M
authors.lastname: Inaji
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nariai
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Ohno
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000209:etiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000209:etiology*; D005849:Gerbillinae; D010474:Percussion / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects; D011743:Pyrimidines / Q000627:therapeutic use*; D013997:Time Factors; 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; D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles