Summary:The tissue concentrations of the monoaminer gic neurotransmitters noradrenaline (NA), dopamine, and serotonin (5-HT) and of their major metabolites were measured by HPLC and electrochemical detection in sev eral rat brain areas after intracerebroventricular injection of streptozotocin (STZ). NA levels were found to be de creased in the frontal cortex by 14%, in the entorhinal cortex by 18%, and in the striatum by 38%. In the ento rhinal cortex, 5-HT levels were decreased by 19% and the 5-HT turnover rate, measured as the 5-hydroxyindoleace-The energy metabolism in the central nervous system and thus normal neuronal function and structure are based on the breakdown of glucose, which is the major fuel for biological energy (Sokoloff, 1977(Sokoloff, , 1980 Siesj6, 1978). In the nonneu ral tissues, glycolytic glucose breakdown and pyru vate oxidation are known to be controlled by insulin and insulin receptors, respectively (Kahn, 1985), but it is not yet clear whether insulin and the insulin receptors have the same functions also in the ner vous tissue. The existence of both insulin mRNA (Young, 1986; Marks et aI., 1990) and insulin recep tors in brain has already been established (Havrank ova et aI., 1978; Hill et aI., 1986; Werther et aI.,

No 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.

To evaluate the development of striatal ischemic cell damage in relation to alterations in dopamine (DA) transmission, one year old male Wistar rats underwent a 15 min incomplete cerebral ischemia (ICI) induced by occlusion of the common carotid arteries and by hypovolemic hypotension. The animals were divided into the following experimental groups: sham operated rats, rats with ICI without reperfusion, and rats with ICI followed by 60 min, 24 h, 72 h and 144 h of recirculation. The ischemia induced striatal lesions were investigated in serial coronal brain sections, stained with cresylviolet or immunostained for dopamine and cAMP regulated phosphoprotein (DARPP-32), for tyrosine hydroxylase (TH) and for glial fibrillary acidic protein (GFAP) immunoreactivities (IR). Measurements of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were made on analogous experimental groups using HPLC methods. Signs of degeneration in small to medium sized neurons were already seen after 60 min of postischemic reperfusion together with slight decreases of DARPP-32 IR and increases of GFAP IR. The damage continued to increase up to 144 h, and after 24 h of recirculation there were clearly defined areas of reduced DARPP-32 IR, overlapping with increased TH IR and increased GFAP IR. The levels of DA, DOPAC and HVA increased sharply after 60 min (151%, 462% and 201%, respectively) remained high after 24 h and normalized after 72 h of recirculation. The DA metabolism was high after 60 min and had already normalized after 24 h of recirculation. The increased DA metabolism in striatal nerve terminals in response to ischemic injury may reflect an early degenerative change in the DA terminals. The long-lasting increase in TH IR may to some extent represent an adaptive change in response to the disappearance of DA receptor-containing nerve cells. Based on the present findings it is possible that an increased D1 transmission in neostriatum immediately following the ischemic injury may contribute to striatal nerve cell degeneration in which an enhancement of NMDA receptor transduction may be implicated.