Document Detail

Leptin attenuates cerebral ischemia injury through the promotion of energy metabolism via the PI3K/Akt pathway.
MedLine Citation:
PMID:  23299243     Owner:  NLM     Status:  MEDLINE    
The purpose of this study was to investigate the protective mechanism of leptin-mediated metabolic recovery against cerebral injury after ischemia and reperfusion. We determined the neurologic deficit score, extent of brain edema, and infarct volume after reperfusion. The histopathologic alterations and changes in glucose uptake in the brain were also observed. Moreover, the levels of lactate dehydrogenase (LDH), lactic acid, pyruvate, and ATP in brain tissue were detected. Leptin levels in serum were also detected. To further define leptin-induced neuroprotective signaling pathways, we examined the levels of phosphorylated Akt (p-Akt) in the brain and in cultured cells. After transient ischemia, leptin treatment markedly reduced the neurologic deficits, cerebral infarct volume, and brain edema. After leptin injection, ATP, leptin, and p-Akt levels were significantly increased, LDH levels and lactic acid/pyruvate ratio were noticeably reduced, and histopathologic injuries were alleviated, which were all reversed by the PI(3)K inhibitor LY294002. These data show that leptin ameliorates cerebral ischemia/reperfusion injury by enhancing p-Akt, which in turn improves the supply of energy. The PI(3)K/Akt pathway was found to be the critical pathway for the mediation of leptin-induced neuroprotection, a finding that may prove to be useful in the treatment of ischemic stroke.
Jinying Zhang; Zihui Deng; Jie Liao; Cuihong Song; Chen Liang; Hui Xue; Luhuan Wang; Kai Zhang; Guangtao Yan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  567-74     Citation Subset:  IM    
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MeSH Terms
Brain Edema / metabolism,  pathology,  prevention & control
Brain Infarction / metabolism,  pathology,  prevention & control*
Chromones / pharmacology
Energy Metabolism / drug effects
Enzyme Inhibitors / pharmacology
L-Lactate Dehydrogenase / metabolism
Lactic Acid / metabolism
Leptin / pharmacology*
Morpholines / pharmacology
Nerve Tissue Proteins / metabolism*
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism*
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / metabolism*
Pyruvic Acid / metabolism
Reperfusion Injury / complications,  drug therapy*,  metabolism,  pathology
Signal Transduction / drug effects*
Reg. No./Substance:
0/Chromones; 0/Enzyme Inhibitors; 0/Leptin; 0/Morpholines; 0/Nerve Tissue Proteins; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 33X04XA5AT/Lactic Acid; 8558G7RUTR/Pyruvic Acid; EC Dehydrogenase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt

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