Delayed neuronal death in hippocampal CA1 pyramidal neurons after forebrain ischemia in hyperglycemic gerbils: amelioration by indomethacin

被引:28
作者
Kondo, F
Kondo, Y
Makino, H
Ogawa, N
机构
[1] Okayama Univ, Sch Med, Dept Neurosci, Inst Mol & Cellular Med, Okayama 7008558, Japan
[2] Okayama Univ, Sch Med, Dept Med 3, Okayama 7008558, Japan
关键词
forebrain ischemia; hyperglycemia; indomethacin; TUNEL; gerbil;
D O I
10.1016/S0006-8993(99)02256-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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/l 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 bur such process is not associated with DNA fragmentation. Our results also showed that indomethacin provides a neuroprotective effect in normo- and hyperglycemic conditions. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:93 / 98
页数:6
相关论文
共 29 条
[1]   ISCHEMIC DELAYED NEURONAL DEATH - A MITOCHONDRIAL HYPOTHESIS [J].
ABE, K ;
AOKI, M ;
KAWAGOE, J ;
YOSHIDA, T ;
HATTORI, A ;
KOGURE, K ;
ITOYAMA, Y .
STROKE, 1995, 26 (08) :1478-1489
[2]   EARLY IMMUNOHISTOCHEMICAL CHANGES OF MICROTUBULE-BASED MOTOR PROTEINS IN GERBIL HIPPOCAMPUS AFTER TRANSIENT ISCHEMIA [J].
AOKI, M ;
ABE, K ;
YOSHIDA, T ;
HATTORI, A ;
KOGURE, K ;
ITOYAMA, Y .
BRAIN RESEARCH, 1995, 669 (02) :189-196
[3]   Ketoprofen, a non-steroidal anti-inflammatory drug prevents the late-onset reduction of muscarinic receptors in gerbil hippocampus after transient forebrain ischemia [J].
Asanuma, M ;
Asanuma, SN ;
GomezVargas, M ;
Yamamoto, M ;
Ogawa, N .
NEUROSCIENCE LETTERS, 1997, 225 (02) :109-112
[4]  
Chen J, 1997, J NEUROCHEM, V69, P232
[5]  
Chen J, 1998, J NEUROSCI, V18, P4914
[6]  
EMARA MK, 1989, DIABETES RES CLIN EX, V12, P189
[7]   IDENTIFICATION OF PROGRAMMED CELL-DEATH INSITU VIA SPECIFIC LABELING OF NUCLEAR-DNA FRAGMENTATION [J].
GAVRIELI, Y ;
SHERMAN, Y ;
BENSASSON, SA .
JOURNAL OF CELL BIOLOGY, 1992, 119 (03) :493-501
[8]   RECOVERY OF POSTISCHEMIC BRAIN METABOLISM AND FUNCTION FOLLOWING TREATMENT WITH A FREE-RADICAL SCAVENGER AND PLATELET-ACTIVATING-FACTOR ANTAGONISTS [J].
GILBOE, DD ;
KINTNER, D ;
FITZPATRICK, JH ;
EMOTO, SE ;
ESANU, A ;
BRAQUET, PG ;
BAZAN, NG .
JOURNAL OF NEUROCHEMISTRY, 1991, 56 (01) :311-319
[9]   INCREASING AGE, DIABETES-MELLITUS AND RECOVERY FROM STROKE [J].
GRAY, CS ;
FRENCH, JM ;
BATES, D ;
CARTLIDGE, NEF ;
VENABLES, GS ;
JAMES, OFW .
POSTGRADUATE MEDICAL JOURNAL, 1989, 65 (768) :720-724
[10]   TIME COURSE OF CHANGES IN LIPID-PEROXIDATION, PRESYNAPTIC AND POSTSYNAPTIC CHOLINERGIC INDEXES, NMDA RECEPTOR-BINDING AND NEURONAL DEATH IN THE GERBIL HIPPOCAMPUS FOLLOWING TRANSIENT ISCHEMIA [J].
HABA, K ;
OGAWA, N ;
MIZUKAWA, K ;
MORI, A .
BRAIN RESEARCH, 1991, 540 (1-2) :116-122