The possible involvement of tetrodotoxin-sensitive ion channels in ischemic neuronal damage in the rat hippocampus.
To determine the role of tetrodotoxin-sensitive ion channels in post-ischemic selective neuronal death, the effect of tetrodotoxin on ischemia-induced brain cell injury was studied in rats. The animals were subjected to 20 min of cerebral ischemia in a four vessels occlusion model. Thirty min before ischemia, tetrodotoxin at a dose of 10(-7) or 10(-6) M was topically applied into the hippocampal CA1 subfield. Morphological changes in the CA1 subfield were evaluated 7 days after ischemia and compared with those of a vehicle-injected group. The average cell density of CA1 pyramidal neurons ipsilateral to the injection (cells/mm, mean +/- S.E.M.) was 27 +/- 7 (n = 6) in the vehicle-treated group, and 56 +/- 13 (n = 6) and 83 +/- 17 (n = 6) in the group treated with tetrodotoxin at doses of 10(-7) and 10(-6) M, respectively. Tetrodotoxin mitigated the ischemic hippocampal neuronal damage in a limited but dose-dependent manner. This suggests that activation of tetrodotoxin-sensitive ion channels might contribute to the process of the ischemic neuronal damage.
Yamasaki
Y
Y
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kogure
K
K
Hara
H
H
Ban
H
H
Akaike
N
N
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D011712:Pyramidal Tracts / Q000166:cytology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000633:toxicity*
D007473:Ion Channels; D013779:Tetrodotoxin