Alterations of Interneurons of the Gerbil Hippocampus after Transient Cerebral Ischemia: Effect of Pitavastatin

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 30; no. 11; pp. 2014 - 2025
• Main Authors: HIMEDA, Toshiki, HAYAKAWA, Natsumi, TOUNAI, Hiroko, SAKUMA, Mio, KATO, Hiroyuki, ARAKI, Tsutomu
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.11.2005; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Cell Count - methods; Disease Models, Animal; Enzyme Inhibitors - administration & dosage; Gerbillinae; Hippocampus - cytology; Immunohistochemistry - methods; Interneurons - drug effects; Interneurons - metabolism; Ischemic Attack, Transient - metabolism; Male; Medical sciences; Neurology; Nitric Oxide Synthase Type I - metabolism; Parvalbumins - metabolism; Quinolines - administration & dosage; Time Factors; Vascular diseases and vascular malformations of the nervous system; Immunohistochemistry; Calcium; Toxicity; Central nervous system; Cardiovascular disease; Inorganic element; Encephalon; Interneuron; Binding protein; Ischemia; HMG-CoA reductase; interneurons; Enzyme; Rodentia; Statin derivative; Parvalbumin; Nitric-oxide synthase; Pitavastatin; Vertebrata; Mammalia; Animal; nNOS; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Gerbil; Hippocampus
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1300798

We investigated the immunohistochemical alterations of parvalbumin (PV)-expressing interneurons in the hippocampus after transient cerebral ischemia in gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the damage of neurons and interneurons in the hippocampus after cerebral ischemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was observed in interneurons of the hippocampal CA1 sector. Furthermore, a significant decrease of PV immunoreactivity was found in interneurons of the hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1 sector up to 14 days after ischemia. Pitavastatin significantly prevented the neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our immunohistochemical study also showed that pitavastatin prevented significant decrease of PV- and nNOS-positive interneurons in the hippocampus after ischemia. Double-labeled immunostainings showed that PV immunoreactivity was not found in nNOS-immunopositive interneurons of the brain. The present study demonstrates that cerebral ischemia can cause a loss of both PV- and nNOS-immunoreactive interneurons in the hippocampal CA1 sector. Our findings also show that the damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our present study indicates that pitavastatin can prevent the damage of interneurons in the hippocampus after cerebral ischemia. Thus, our study provides valuable information for the pathogenesis after cerebral ischemia.