Leptin Attenuates Cerebral Ischemia Injury through the Promotion of Energy Metabolism via the PI3K/Akt Pathway. Issue 4 (April 2013)

• Record Type: Journal Article
• Authors: Zhang, Jinying; Deng, Zihui; Liao, Jie; Song, Cuihong; Liang, Chen; Xue, Hui; Wang, Luhuan; Zhang, Kai; Yan, Guangtao
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 33:Issue 4(2013)
• Page Start: 567
• Page End: 574
• Publication Date: 2013-04
• Subjects: Akt pathway -- cerebral ischemia -- energy metabolism -- leptin -- neuroprotection -- PI3K -- reperfusion -- stroke; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2012.202
• Languages: English
• ISSNs: 0271-678X

Abstract

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 PI3 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 PI3 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.