PMID- 12677021
OWN - NLM
STAT- MEDLINE
DCOM- 20030630
LR  - 20161122
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 34
IP  - 5
DP  - 2003 May
TI  - Chronic treatment with a low dose of lithium protects the brain against ischemic 
      injury by reducing apoptotic death.
PG  - 1287-92
AB  - BACKGROUND AND PURPOSE: In vitro and in vivo studies have demonstrated 
      neuroprotective actions of lithium. The present study investigated the effect of 
      a low dose of lithium on infarct volume and neurological outcome as well as on 
      apoptotic and inflammatory processes in rats exposed to focal ischemia. METHODS: 
      Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 
      minutes followed by reperfusion. Lithium (1 mmol/kg) was given subcutaneously 
      daily for 14 days before the onset of MCAO and 2 days thereafter. Blood 
      parameters and cerebral blood flow were assessed before, during, and after MCAO. 
      Rats were examined for neurological deficits 24 and 48 hours after MCAO. Two days 
      after MCAO, the brains were removed for immunohistochemical evaluation of 
      caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling 
      (TUNEL), activated microglia, and the expression of AP-1 proteins (c-Fos and 
      c-Jun). Infarct volume was assessed by cresyl violet staining. RESULTS: 
      Pretreatment with lithium did not alter cerebral blood flow or blood parameters. 
      Neurological deficits were significantly decreased in rats treated with lithium 
      at 24 and 48 hours after ischemia. Infarct volume was reduced in rats treated 
      with lithium at 48 hours after ischemia. Lithium significantly decreased the 
      ischemia-induced caspase-3 immunoreactivity and TUNEL staining as well as the 
      AP-1 protein expression in the penumbra of the ischemic cortex. No changes in 
      activated microglia were observed. CONCLUSIONS: The present study demonstrates 
      that chronic treatment with lithium at a low dose exhibits neuroprotection in 
      transient focal cerebral ischemia. Antiapoptotic mechanisms are involved in the 
      lithium-induced neuroprotective effects.
FAU - Xu, Jihong
AU  - Xu J
AD  - Institute of Pharmacology, Christian-Albrechts University of Kiel, Germany.
FAU - Culman, Juraj
AU  - Culman J
FAU - Blume, Annegret
AU  - Blume A
FAU - Brecht, Stephan
AU  - Brecht S
FAU - Gohlke, Peter
AU  - Gohlke P
LA  - eng
PT  - Journal Article
DEP - 20030403
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Biomarkers)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Transcription Factor AP-1)
RN  - 2BMD2GNA4V (Lithium Carbonate)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Biomarkers
MH  - Brain Edema/etiology/pathology/prevention & control
MH  - Brain Ischemia/*drug therapy/etiology/pathology
MH  - Caspase 3
MH  - Caspases/analysis
MH  - Cerebrovascular Circulation/drug effects
MH  - Depression, Chemical
MH  - Drug Administration Schedule
MH  - Drug Evaluation, Preclinical
MH  - In Situ Nick-End Labeling
MH  - Infarction, Middle Cerebral Artery/complications/*drug therapy/pathology
MH  - Lithium Carbonate/administration & dosage/*therapeutic use
MH  - Male
MH  - Microglia/pathology
MH  - Nerve Tissue Proteins/analysis
MH  - Neuroprotective Agents/administration & dosage/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/prevention & control
MH  - Single-Blind Method
MH  - Transcription Factor AP-1/analysis
EDAT- 2003/04/05 05:00
MHDA- 2003/07/02 05:00
CRDT- 2003/04/05 05:00
PHST- 2003/04/05 05:00 [pubmed]
PHST- 2003/07/02 05:00 [medline]
PHST- 2003/04/05 05:00 [entrez]
AID - 01.STR.0000066308.25088.64 [pii]
AID - 10.1161/01.STR.0000066308.25088.64 [doi]
PST - ppublish
SO  - Stroke. 2003 May;34(5):1287-92. doi: 10.1161/01.STR.0000066308.25088.64. Epub 
      2003 Apr 3.