An investigation of the neuroprotective effect of lithium in organotypic slice cultures of rat hippocampus exposed to oxygen and glucose deprivation.
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.
Cimarosti
H
H
Departamento de BioquImica, Instituto de Ciências Básicas da Saúde, UFRGS, 90035-003, Porto Alegre, Brazil.
Rodnight
R
R
Tavares
A
A
Paiva
R
R
Valentim
L
L
Rocha
E
E
Salbego
C
C
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D016923:Cell Death; D015687:Cell Hypoxia; D003470:Culture Media; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005453:Fluorescence; D005947:Glucose / Q000172:deficiency*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D015151:Immunoblotting; D018021:Lithium Chloride / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018692:Antimanic Agents; D003470:Culture Media; D018691:Excitatory Amino Acid Antagonists; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D018021:Lithium Chloride; D005947:Glucose