期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 32, 期 6, 页码 1086-1096出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2012.30
关键词
hypoglycemia; lactate; microglial activation; neuron death; superoxide
资金
- Hallym University [HRF-201202-004]
- Korea Science and Engineering Foundation [KOSEF-2009-0078399]
- Ministry of Health & Welfare, Republic of Korea [A100687]
- Korea Health Promotion Institute [A100687] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by similar to 80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD. due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1086-1096; doi:10.1038/jcbfm.2012.30; published online 28 March 2012
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据