Acute effects of irradiation on the rat brain: protection by glutamate blockade

Abstract

Riluzole (2-amino-6-trifluorothethoxy benzothiazole), dizocilpine (MK-801; (+)-5-methyl-10,11-dihydro-5 H-dibenzo( a,d)-cyclohepten-5,10-imine maleate), and lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2-triazine), agents reported to have neuroprotective actions, and WR2721 ( S-2-(3-aminopropylamino)-ethylphosphorothioic acid), a radioprotector, were evaluated in 15-day-old rats that underwent a 2.5 Gray (Gy) irradiation from a cobalt 60 source. 20 min after irradiation, riluzole (0.5–8 mg/kg), dizocilpine (0.1–1 mg/kg), lamotrigine (25 mg/kg), WR 2721 (75 mg/kg) or vehicle, were injected intraperitoneally. 6 h after irradiation, behavioural and histological evaluations revealed that exposure to 2.5 Gy caused hypolocomotion, stumbling gait and somnolence, which was significantly reduced, from the dose of 4 mg/kg i.p. of riluzole. A dose-dependent protection of neurones in the dentate gyrus, starting from the dose of 1 mg/kg i.p. was also seen. Dizocilpine caused behavioural modifications but significantly reduced neuronal damage. Lamotrigine significantly increased neuronal damage while WR 2721 conferred no protection. In conclusion, two blockers of glutamatergic neurotransmission conferred significant protection against brain damage caused by ionizing irradiation when administered subsequent to exposure.