An investigation of the neuroprotective effect of lithium in organotypic slice cultures of rat hippocampus exposed to oxygen and glucose deprivation

被引:60
作者
Cimarosti, H [1 ]
Rodnight, R [1 ]
Tavares, A [1 ]
Paiva, R [1 ]
Valentim, L [1 ]
Rocha, E [1 ]
Salbego, C [1 ]
机构
[1] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, BR-90035003 Porto Alegre, RS, Brazil
关键词
cerebral ischemia; lithium; HSP27; organotypic culture; oxygen/glucose deprivation; neuroprotection; hippocampus;
D O I
10.1016/S0304-3940(01)02310-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Brain ischemia results in cellular degeneration and loss of function. Here we investigated the neuroprotective effect of lithium in an in vitro model of ischemia. Organotypic hippocampal slice cultures were exposed to oxygen and glucose deprivation. Cellular death was quantified by measuring uptake of propidium iodide (PI). Lithium chloride (0.2-1.2 mM) was added to the medium before, during and after lesion induction. A decrease in incorporation of PI was observed, indicating a neuroprotective effect in all doses tested. We also studied the effect of lithium on the phosphorylation of HSP27, a heat shock protein involved in cellular protection in its dephosphorylated state. In the lesioned hippocampus, 0.4 mM lithium chloride decreased the proportion of phosphorylated HSP27 to total HSP27. These results suggest that lithium may be useful in the treatment of brain ischemia. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:33 / 36
页数:4
相关论文
共 21 条
[1]   Inhibition of different pathways influencing Na+ homeostasis protects organotypic hippocampal slice cultures from hypoxic/hypoglycemic injury [J].
Breder, J ;
Sabelhaus, CF ;
Opitz, T ;
Reymann, KG ;
Schröder, UH .
NEUROPHARMACOLOGY, 2000, 39 (10) :1779-1787
[2]   Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons [J].
Chalecka-Franaszek, E ;
Chuang, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (15) :8745-8750
[3]   Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression - A prominent role in neuroprotection against excitotoxicity [J].
Chen, RW ;
Chuang, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6039-6042
[4]  
Imura T, 1999, J NEUROSCI, V19, P9768
[5]  
JAKOB U, 1993, J BIOL CHEM, V268, P1517
[6]   A simple in vitro model of ischemia based on hippocampal slice cultures and propidium iodide fluorescence [J].
Laake, JH ;
Haug, FM ;
Wieloch, T ;
Ottersen, OP .
BRAIN RESEARCH PROTOCOLS, 1999, 4 (02) :173-184
[7]   PHOSPHORYLATION OF HSP27 DURING DEVELOPMENT AND DECAY OF THERMOTOLERANCE IN CHINESE-HAMSTER CELLS [J].
LANDRY, J ;
CHRETIEN, P ;
LASZLO, A ;
LAMBERT, H .
JOURNAL OF CELLULAR PHYSIOLOGY, 1991, 147 (01) :93-101
[8]   Lithium at 50: Have the neuroprotective effects of this unique cation been overlooked? [J].
Manji, HK ;
Moore, GJ ;
Chen, G .
BIOLOGICAL PSYCHIATRY, 1999, 46 (07) :929-940
[9]   Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx [J].
Nonaka, S ;
Hough, CJ ;
Chuang, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (05) :2642-2647
[10]   Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats [J].
Nonaka, S ;
Chuang, DM .
NEUROREPORT, 1998, 9 (09) :2081-2084