Age influences abnormalities in striatal dopamine metabolism during and after transient forebrain ischemia

Abstract

Age has been found to be a significant risk factor for brain ischemia and its mortality. After cerebral ischemia, the nigrostriatal dopaminergic system undergoes selective vulnerability with necrosis of striatal neurons. To study the effect of age and transient forebrain ischemia on striatal dopamine metabolism, investigations were performed in 1-year-old (adult) and 2-year-old (aged) male Wistar rats. A 15 min period of bilateral transient incomplete ischemia (ICI) was induced, and the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were measured in the striatum by means of HPLC and electrochemical detection at the end of ischemia without reperfusion, and after 1 h, 24 h, 72 h, 144 h, and 288 h of postischemic cerebral reperfusion. In normal conditions, no 3-MT was detectable in either age group studied, and no other age-related changes could be found in DA or its metabolites. During ICI, an age-related difference became obvious in the 3-MT concentration, which was higher in aged animals. In this group, DOPAC dropped and DA turnover increased. After 1 h of postischemic reperfusion, the concentrations of DOPAC and HVA, as well as the turnover rate, had increased in both age groups, whereas an increase in the DA concentration became apparent in the adult animals only. The enhancement of the concentration of both DOPAC and HVA was more marked in adult animals than in aged ones. At 24 h of postischemic cerebral reperfusion, DA concentration was still elevated in both age groups, and HVA in the 1-year-old animals only. At 72 h of postischemic cerebral reperfusion, no differences were obvious between adult experimental animals and controls, whereas the elevated DA concentration persisted in aged animals, being higher than in the control group and in the 1-year-old rats. DA turnover was reduced. Longer periods of postischemic cerebral reperfusion were not found to be followed by any abnormalities compared with controls except for the DA concentration at 288 h (1-year-old group); nor were there any differences between the two age groups studied. The data obtained in this investigation clearly indicate age-related differences in the striatal dopaminergic neurotransmission after transient cerebral ischemia, in that in the aged brain reactions are markedly delayed after an injurious event such as ischemia.