Lithium reduces ischemia-induced hippocampal CA1 damage and behavioral deficits in gerbils

Brain Res. 2007 Dec 12:1184:270-6. doi: 10.1016/j.brainres.2007.09.054. Epub 2007 Sep 29.


Lithium is a major drug used for the treatment of bipolar mood disorder and has recently been shown to have neuroprotective properties. In this study we investigated the neuroprotective effects of lithium in gerbils subjected to global cerebral ischemia, an animal model of stroke. The ischemia-induced exploratory behavior changes, measured by open field testing, were largely suppressed by lithium treatment for 7 days prior to ischemic onset. Similarly, memory impairments, measured by T-maze testing, were prevented by lithium pretreatment. This is believed to be the first report of lithium-induced protection against hyperactivity in a novel open field and memory impairment in a gerbil model of global ischemia. These behavioral benefits were associated with an increase in viable cells as measured by hematoxylin and eosin staining and a decrease in apoptotic TUNEL-positive cells in the CA1 hippocampal area of ischemic gerbils. Moreover, the lithium-induced neuroprotection was accompanied by down-regulation of pro-apoptotic p53 in the CA1 but up-regulation of anti-apoptotic Bcl-2 and heat shock protein 70 (HSP70) in the ischemic brain. These results underscore the ability of lithium to improve functional behavioral outcome in gerbil and rodent cerebral ischemic models and further indicate the potential therapeutic use of lithium in certain human stroke conditions.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use*
  • Behavior, Animal
  • Behavioral Symptoms / etiology
  • Behavioral Symptoms / prevention & control*
  • Brain Injuries / pathology*
  • Brain Injuries / prevention & control*
  • Cell Death / drug effects
  • Gerbillinae
  • HSP70 Heat-Shock Proteins / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • In Situ Nick-End Labeling / methods
  • Ischemia / complications
  • Lithium Compounds / blood
  • Lithium Compounds / therapeutic use*
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism


  • Antipsychotic Agents
  • HSP70 Heat-Shock Proteins
  • Lithium Compounds
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53