Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia

被引:37
作者
Denes, L. [1 ]
Szilagyi, G. [1 ]
Gal, A. [1 ]
Nagy, Z. [1 ]
机构
[1] Natl Inst Psychiat & Neurol, Dept Vasc Neurol, Cell Biol Lab, H-1026 Budapest, Hungary
关键词
apoptosis; TUNEL; caspase-3; transient MCA occlusion; talampanel; mice;
D O I
10.1016/j.brainresbull.2006.02.024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Talampanel (IVAX) is a non-competitive AMPA-antagonist has a remarkable neuroprotection in different rodent stroke models. The focal cerebral ischemia in mice was induced by transient (60 min.) MCA occlusion and 48 h reperfusion and treated with talampanel (6 x 2 mg/kg, i.p.). The apoptotic and necrotic cells were analyzed by double immune histochemical staining on confocal laser microscope. The infarct size is decreased significantly by talampanel treatment (from 57.1 +/- 7.2 mm(2) to 18.9 +/- 2.6 mm(2), p < 0.001). The number of TUNEL-positive cells localized mostly in the border zone of ischemic lesions is significantly decreased after talampanel treatment (from 962 +/- 13.0 to 604 +/- 6.9, p < 0.01). A strong, significant reduction of caspase-3 active cells was visualized. Talampanel as a neuroprotective drug candidate has a significant effect in mice transient MCA occlusion model. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:260 / 262
页数:3
相关论文
共 12 条
[1]  
Anversa P, 1998, BASIC RES CARDIOL, V93, P8
[2]   Presence of double-strand breaks with single-base 3' overhangs in cells undergoing apoptosis but not necrosis [J].
Didenko, VV ;
Hornsby, PJ .
JOURNAL OF CELL BIOLOGY, 1996, 135 (05) :1369-1376
[3]   Pathobiology of ischaemic stroke: an integrated view [J].
Dirnagl, U ;
Iadecola, C ;
Moskowitz, MA .
TRENDS IN NEUROSCIENCES, 1999, 22 (09) :391-397
[4]   GYKI 52466, A 2,3-BENZODIAZEPINE, IS A HIGHLY SELECTIVE, NONCOMPETITIVE ANTAGONIST OF AMPA/KAINATE RECEPTOR RESPONSES [J].
DONEVAN, SD ;
ROGAWSKI, MA .
NEURON, 1993, 10 (01) :51-59
[5]   Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart [J].
Dumont, EA ;
Reutelingsperger, CPM ;
Smits, JFM ;
Daemen, MJAP ;
Doevendans, PAF ;
Wellens, HJJ ;
Hofstra, L .
NATURE MEDICINE, 2001, 7 (12) :1352-1355
[6]   The AMPA-antagonist talampanel is neuroprotective in rodent models of focal cerebral ischemia [J].
Erdö, F ;
Berzenyi, P ;
Andrási, F .
BRAIN RESEARCH BULLETIN, 2005, 66 (01) :43-49
[7]   Immunohistochemical analysis of protein expression after middle cerebral artery occlusion in mice [J].
Erdö, F ;
Trapp, T ;
Mies, G ;
Hossmann, KA .
ACTA NEUROPATHOLOGICA, 2004, 107 (02) :127-136
[8]   Prolonged therapeutic window for ischemic brain damage caused by delayed caspase activation [J].
Fink, K ;
Zhu, JM ;
Namura, S ;
Shimizu-Sasamata, M ;
Endres, M ;
Ma, JY ;
Dalkara, T ;
Yuan, JY ;
Moskowitz, MA .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1998, 18 (10) :1071-1076
[9]   Non-NMDA mechanism in the inhibition of cellular apoptosis and memory impairment induced by repeated ischemia in rats [J].
Iwasaki, K ;
Chung, EH ;
Egashira, E ;
Hatip-Al-Khatib, I ;
Mishima, K ;
Egawa, T ;
Irie, K ;
Fujiwara, M .
BRAIN RESEARCH, 2004, 995 (01) :131-139
[10]   AMPA receptor-mediated toxicity in oligodendrocyte progenitors involves free radical generation and activation of JNK, calpain and caspase 3 [J].
Liu, HN ;
Giasson, BI ;
Mushynski, WE ;
Almazan, G .
JOURNAL OF NEUROCHEMISTRY, 2002, 82 (02) :398-409