Exo-focal postischemic neuronal damage in the rat brain: alteration of [3H]forskolin binding using in vitro autoradiography.
We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [3H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [3H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [3H]forskolin binding sites was observed in the ipsilateral substantial nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. The delayed reduction of [3H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci.
Nagasawa
H
H
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kogure
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002132:Calcium Radioisotopes; D002536:Cerebral Arteries / Q000502:physiology; D005576:Colforsin / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D002132:Calcium Radioisotopes; D005576:Colforsin; D000262:Adenylyl Cyclases