Involvement of glial endothelin/nitric oxide in delayed neuronal death of rat hippocampus after transient forebrain ischemia.
1. We examined time- and cell-type-dependent changes in endothelin (ET)-1-like immunoreactivity, ET receptors binding and nitric oxide (NO) synthase (NOS) activity in CA1 subfields of the hippocampus of stroke-prone spontaneously hypertensive rats subjected to a 10-min bilateral carotid occlusion and reperfusion. 2. Microglia aggregated in accord with neuronal death and expressed a high density of ET(B) receptors and an intense NOS activity in the damaged CA1 pyramidal cell layer, 7 days after the induced transient forebrain ischemia. The increased NOS activity and ET(B) receptor in microglia disappeared 28 days after this transient ischemia. 3. In contrast to microglia, astrocytes presented a moderate level of ET-1-like immunoreactivity, ET(B) receptors, and NOS activity in all areas of the damaged CA1 subfields, 7 days after the ischemia. These events were further enhanced 28 days after the ischemia. 4. In light of these findings, the possibility that the microglial and the astrocytic ET(B)/NO system largely contributes to development of the neuronal death and to reconstitution of the damaged neuronal tissue, respectively, in the hippocampus subjected to a transient forebrain ischemia would have to be considered.
Department of Pharmacology, Nagasaki University School of Medicine, Sakamoto, Japan.
K
K
Yamashita
Y
Y
Kataoka
Y
Y
Sakurai-Yamashita
K
K
Shigematsu
A
A
Himeno
M
M
Niwa
K
K
Taniyama
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology; D007457:Iodine Radioisotopes; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017628:Microglia / Q000737:chemistry / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000032:analysis; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR
D019332:Endothelin-1; D007457:Iodine Radioisotopes; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase