Autoradiographic analysis of second messenger and neurotransmitter receptor bindings in the strionigral system of the postischemic rat brain.
We studied the postischemic alterations of second messenger and receptor systems focusing on the strionigral pathway in order to clarify the mechanism of the delayed neuronal changes in remote areas of the rat brain after transient focal ischemia. Chronological changes of [3H]forskolin and [3H]SCH 23390 binding sites and 45Ca accumulation were determined by using autoradiographic methods after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. After the ischemic insult, 45Ca accumulation extended to the lateral segment of the caudate putamen (CPu-L) and to the cerebral cortex, both supplied by the occluded MCA. After the ischemia, [3H]forskolin binding sites were found to be markedly decreased in the early stage in the CPu-L, the ischemic focus in this model, but reduction of the dopamine D-1 receptor sites was first detected there 1 day after the ischemia. On the contrary, in the exo-focal remote areas, there was no alteration of either [3H]forskolin or D-1 receptor binding sites on day 1. However, 3 days after the ischemia, marked reduction of both these binding sites was first observed in the ipsilateral substantia nigra, which had not been directly affected by the original ischemic insult. These postischemic delayed phenomena observed in the substantia nigra developed concurrently with abnormal 45Ca accumulation. These results suggest that strionigral terminal degeneration in the substantia nigra is caused by precedent ischemic damage of the ipsilateral caudate putamen and that intracellular signal transduction including both second messenger and receptor systems may be involved prior to the neuronal damage in the exo-focal postischemic brain areas.
Nagasawa
H
H
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Araki
T
T
Kogure
K
K
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002339:Carotid Arteries / Q000502:physiology; D005576:Colforsin / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology*; D013378:Substantia Nigra / Q000378:metabolism*
D001552:Benzazepines; D002132:Calcium Radioisotopes; D017447:Receptors, Dopamine D1; D017981:Receptors, Neurotransmitter; D005576:Colforsin