Delayed neuronal death in hippocampal CA1 pyramidal neurons after forebrain ischemia in hyperglycemic gerbils: amelioration by indomethacin.
Hyperglycemia worsens ischemic-induced neuronal damage. Many reports argue the delayed neuronal cell death (DND) after forebrain ischemia in gerbils is due to apoptosis. We examined the effects of hyperglycemia and indomethacin on DND after forebrain ischemia in gerbils. Complete occlusion of both common carotid arteries was performed for 3.5 min followed by declamping and reperfusion. Blood glucose levels were maintained at 25-30 mmol/1 for 24 h after reperfusion in the hyperglycemic groups. We examined morphological changes consistent with DND using Nissel-stained sections and DNA fragmentation using TUNEL staining, at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 h, and 7 days after reperfusion. DND was noted 96-120 h after ischemia in normoglycemic group. Hyperglycemia enhanced the development of DND at an earlier stage (48-84 h after ischemia). TUNEL positive neurons were detected 72-108 h after reperfusion in normoglycemic group, but very few TUNEL positive neurons were detected in hyperglycemic group at 36-48 h. Indomethacin reduced the number of TUNEL-positive cells in normoglycemia and completely inhibited the appearance of TUNEL-positive cells under hyperglycemia. The number of viable neurons at 7 days after ischemia was markedly higher in indomethacin-treated groups than vehicle-treated group. Our results indicate that hyperglycemia worsens DND after forebrain ischemia in gerbils but such process is not associated with DNA fragmentation. Our results also showed that indomethacin provides a neuroprotective effect in normo- and hyperglycemic conditions.
Kondo
F
F
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, 2-5-1 Shikatacho, Okayama, Japan. kondor@cc.okayama-u.ac.jp
Kondo
Y
Y
Makino
H
H
Ogawa
N
N
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis; D016923:Cell Death / Q000187:drug effects; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006943:Hyperglycemia / Q000150:complications; D020287:In Situ Nick-End Labeling; D007213:Indomethacin / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016548:Prosencephalon / Q000098:blood supply; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin