Neuroprotective effect of 8-OH-DPAT in global cerebral ischemia assessed by stereological cell counting

被引:26
作者
Torup, L
Moller, A
Sager, TN
Diemer, NH
机构
[1] H Lundbeck AS, Dept Neurodegenerat Disorders, DK-2500 Copenhagen, Denmark
[2] NeuroSearch AS, Dept Pharmacol, Pederstrup, Denmark
[3] Univ Copenhagen, Inst Mol Pathol, Neuropathol Lab, DK-2100 Copenhagen, Denmark
[4] Neurosci Pharmabiotech Ctr, DK-2100 Copenhagen, Denmark
关键词
cerebral ischemia; 5-HT receptor; 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin); stereology; (rat);
D O I
10.1016/S0014-2999(00)00175-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The neuroprotective effect of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was tested in a 2-vessel occlusion model in rats. The post-ischemic core temperature was carefully monitored for 24 h. After 7 days of survival, the viable CA1 neurons were counted in an 8-OH-DPAT (125 mu g/kg/h) and vehicle-treated group using the optical fractionator method. The vehicle-treated ischemic rats had a median number of dorsal CAI neurons of 49,900 whereas the 8-OH-DPAT-treated ischemic rats had a significant lower median number of dorsal CAI neurons 105,200 (P = 0.018). 8-OH-DPAT significantly lowered the core temperature compared to the vehicle-treated group during the 24-h post-ischemic period. Hypothermia is proposed as a possible explanation of the neuroprotective effect of 8-OH-DPAT. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:137 / 141
页数:5
相关论文
共 29 条
[1]   A MOUSE MODEL OF FOCAL CEREBRAL-ISCHEMIA FOR SCREENING NEUROPROTECTIVE DRUG EFFECTS [J].
BACKHAUSS, C ;
KARKOUTLY, C ;
WELSCH, M ;
KRIEGLSTEIN, J .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1992, 27 (01) :27-32
[2]  
BIELENBERG GW, 1990, STROKE, V21, P161
[3]   DIRECT EVIDENCE FOR AN IMPORTANT SPECIES-DIFFERENCE IN THE MECHANISM OF 8-OH-DPAT-INDUCED HYPOTHERMIA [J].
BILL, DJ ;
KNIGHT, M ;
FORSTER, EA ;
FLETCHER, A .
BRITISH JOURNAL OF PHARMACOLOGY, 1991, 103 (04) :1857-1864
[4]  
BODEGREUEL KM, 1990, STROKE, V21, P164
[5]   CONDITIONS FOR PHARMACOLOGIC EVALUATION IN THE GERBIL MODEL OF FOREBRAIN ISCHEMIA [J].
CLIFTON, GL ;
TAFT, WC ;
BLAIR, RE ;
CHOI, SC ;
DELORENZO, RJ .
STROKE, 1989, 20 (11) :1545-1552
[6]   THE PHARMACOLOGY OF THE BEHAVIORAL AND HYPOTHERMIC RESPONSES OF RATS TO 8-HYDROXY-2-(DI-NORMAL-PROPYLAMINO)TETRALIN (8-OH-DPAT) [J].
GOODWIN, GM ;
DESOUZA, RJ ;
GREEN, AR ;
HEAL, DJ .
PSYCHOPHARMACOLOGY, 1987, 91 (04) :506-511
[7]   THE NEW STEREOLOGICAL TOOLS - DISECTOR, FRACTIONATOR, NUCLEATOR AND POINT SAMPLED INTERCEPTS AND THEIR USE IN PATHOLOGICAL RESEARCH AND DIAGNOSIS [J].
GUNDERSEN, HJG ;
BAGGER, P ;
BENDTSEN, TF ;
EVANS, SM ;
KORBO, L ;
MARCUSSEN, N ;
MOLLER, A ;
NIELSEN, K ;
NYENGAARD, JR ;
PAKKENBERG, B ;
SORENSEN, FB ;
VESTERBY, A ;
WEST, MJ .
APMIS, 1988, 96 (10) :857-881
[9]   A VERSATILE AND SIMPLE METHOD FOR STAINING NERVOUS-TISSUE USING GIEMSA DYE [J].
INIGUEZ, C ;
GAYOSO, MJ ;
CARRERES, J .
JOURNAL OF NEUROSCIENCE METHODS, 1985, 13 (01) :77-86
[10]   MOBILITIES OF HYDROGEN IN SOLVENT-SWOLLEN COALS - A STUDY BY PULSED NMR [J].
KAMIENSKI, B ;
PRUSKI, M ;
GERSTEIN, BC ;
GIVEN, PH .
ENERGY & FUELS, 1987, 1 (01) :45-50