Increased pentose phosphate pathway flux after clinical traumatic brain injury:: a [1,2-13C2]glucose labeling study in humans

被引:94
作者
Dusick, Joshua R.
Glenn, Thomas C.
Lee, Wn Paul
Vespa, Paul M.
Kelly, Daniel F.
Lee, Stefan M.
Hovda, David A.
Martin, Neil A.
机构
[1] Univ Calif Los Angeles, Med Ctr, Div Neurosurg, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Med Ctr, Cerebral Blood Flow Lab, Los Angeles, CA 90095 USA
[3] Harbor UCLA Med Ctr, Div Endocrinol, Torrance, CA 90509 USA
[4] Los Angeles Biomed Res Inst, Torrance, CA 90509 USA
[5] Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA USA
[6] Univ Calif Los Angeles, Brain Injury Res Ctr, Los Angeles, CA USA
关键词
glucose; hyperglycolysis; lactate; metabolism; pentose phosphate cycle; traumatic brain injury;
D O I
10.1038/sj.jcbfm.9600458
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Patients with traumatic brain injury (TBI) routinely exhibit cerebral glucose uptake in excess of that expected by the low levels of oxygen consumption and lactate production. This brings into question the metabolic fate of glucose. Prior studies have shown increased flux through the pentose phosphate cycle (PPC) during cellular stress. This study assessed the PPC after TBI in humans. [1,2-C-13(2)]glucose was infused for 60 mins in six consented, severe-TBI patients (GCS<9) and six control subjects. Arterial and jugular bulb blood sampled during infusion was analyzed for C-13-labeled isotoporners of lactate by gas chromatography/mass spectroscopy. The product of lactate concentration and fractional abundance of isotoporners was used to determine blood concentration of each isotopomer. The difference of jugular and arterial concentrations determined cerebral contribution. The formula PPC=(m1/m2)/(3+(m1/m2)) was used to calculate PPC flux relative to glycolysis. There was enrichment of [1,2-C-13(2)]glucose in arterial-venous blood (enrichment averaged 16.6% in TBI subjects and 28.2% in controls) and incorporation of C-13- label into lactate, showing metabolism of labeled substrate. The PPC was increased in TBI patients relative to controls (19.6 versus 6.9%, respectively; P= 0.002) and was excellent for distinguishing the groups (AUC=0.944, P<0.0001). No correlations were found between PPC and other clinical parameters, although PPC was highest in patients studied within 48 of injury (averaging 33% versus 13% in others; P= 0.0006). This elevation in the PPC in the acute period after severe TBI likely represents a shunting of substrate into alternative biochemical pathways that may be critical for preventing secondary injury and initiating recovery.
引用
收藏
页码:1593 / 1602
页数:10
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