Share：
Share this content in WeChat
X
[Chinese][PDF]83777
• Original Article •
Changes in lactate and associated transporters expression in basal ganglia following hypoxic-ischemic brain injury in piglets
ZHENG Yang  WANG Xiao-ming 

DOI:10.12015/issn.1674-8034.2017.01.011.


[Abstract] Objective: To investigate the expression characteristics of lactate and associated transporters in basal ganglia following hypoxic-ischemic reperfusion brain injury in a piglet model.Materials and Methods: A total of 35 healthy piglets (3—5 days old, 1.0—1.5 kg) were selected. They were divided into control (n=5) and hypoxic-ischemic (HI) model groups (n=30). The HI model group was further divided into six groups according to 1H-magnetic resonance spectroscopy (1H-MRS) scan times after HI (0-2 h, 2-6 h, 6—12 h, 12—24 h, 24-48 h and 48—72 h; n=5/group). The HI model was established by bilateral common carotid artery occlusion and simultaneous hypoxia treatment for 40 min. Piglets in the control group received the same surgical procedure without the hypoxia-ischemia process. 1H-MRS imaging was performed at various time points after HI. The right basal ganglia was the region of interest (ROI) in 1H-MRS imaging for which data was processed by LcModel software. Animals were euthanized immediately after the last scan and the whole brain was quickly removed and bilateral hemispheres separated. The right hemisphere was used for the pathological examination and immunohistochemical staining of monocarboxylate transporters (MCTs). ANOVA analyses were conducted. P<0.05 represented statistical significance.Results: (1) The lactate level became reduced after an initial increase, with the maximal level occurring around 2—6 h following HI. (2) The expression of both MCT-2 and MCT-4 in the basal ganglia initially reached a peak value at 12—24 h and decreased thereafter and they were significantly different at 12-24 h after HI compared to the control group and the other time points of the HI model group (P<0.05).Conclusions: These results indicate that lactate content has potential to regulate the expression of its related transporters in neuronal and glial cell and they have a synergistic effect on the energy metabolism following hypoxic-ischemic reperfusion brain injury.
[Keywords] Brain；Hypoxia-ischemia；Lactate；Piglet；Magnetic resonance spectroscopy

ZHENG Yang Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China

WANG Xiao-ming* Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China

*Correspondence to: Wang XM, E-mail: wangxm024@163.com

Conflicts of interest   None.

ACKNOWLEDGMENTS  This study was supported by National Natural Science Foundation of China NO. 30570541, 30770632, 81271631
Received  2016-11-15
Accepted  2016-12-08
DOI: 10.12015/issn.1674-8034.2017.01.011
DOI:10.12015/issn.1674-8034.2017.01.011.

[1]
Liu Y, Jissendi-Tchofo P, Metens T.足月儿缺氧缺血性脑病的常规MRI、DWI、DTI及MRS表现．磁共振成像, 2011, 2(1):13-18.
[2]
Zhang Y, Hao D, Lv X, et al. Quantification of MRI and MRS characteristics changes in a rat model at different stage of cerebral ischemia. Neurol Res, 2016, 38(7): 640-646.
[3]
Hapuarachchi T, Moroz T, Bainbridge A, et al. Simulating NIRS and MRS measurements during cerebral hypoxia-ischaemia in piglets using a computational model. Adv Exp Med Biol, 2014, 812: 187-193.
[4]
Wang HW, Wang XM, Guo QY. The correlation between DTI parameters and levels of AQP-4 in the early phases of cerebral edema after hypoxic-ischemic/reperfusion injury in piglets. Pediatr Radiol, 2012, 42(8): 992-999.
[5]
Distefano G, Praticò AD. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy. Ital J Pediatr, 2010, 36: 63.
[6]
Dienel GA. Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations. J Cereb Blood Flow Metab, 2014, 34(11): 1736-1748.
[7]
Mächler P, Wyss MT, Elsayed M, et al. In Vivo evidence for a lactate gradient from astrocytes to neurons. Cell Metab, 2016, 23(1): 94-102.
[8]
Bouzat P, Oddo M. Lactate and the injured brain: friend or foe? Curr Opin Crit Care, 2014, 20(2): 133-140.
[9]
Pierre K, Pellerin L, Debernardi R, et al. Cell specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neurosci, 2000, 100 (3): 617-627.
[10]
Pellerin L, Magistretti PJ. How to balance the brain energy budget while spending glucose differently. J Physiol, 2003, 546(2): 235.
[11]
Munkeby BH, De Lange C, Emblem KE, et al. A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging. Acta Radiol, 2008, 49(9): 1049-1057.
[12]
Li YK, Liu GR, Zhou XG, et al. Experimental hypoxic-ischemic encephalopathy: comparison of apparent diffusion coefficients and proton magnetic resonance spectroscopy. Magn Reson Imaging, 2010, 28(4): 487-494.
[13]
Ghosh A, Highton D, Kolyva C, et al. Hyperoxia results in increased aerobic metabolism following acute brain injury. J Cereb Blood Flow Metab, 2016. DOI:
[14]
Dickey EJ, Long SN, Hunt RW. Hypoxic ischemic encephalopathy--what can we learn from humans? J Vet Intern Med, 2011, 25(6): 1231-1240.
[15]
Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy. J Biomed Biotechnol, 2011: 609813.
[16]
Carpenter KL, Jalloh I, Hutchinson PJ. Glycolysis and the significance of lactate in traumatic brain injury. Front Neurosci, 2015, 9: 112.
[17]
Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev, 2007, 54(1): 34-66.
[18]
Chiry O, Fishbein WN, Merezhinskaya N, et al. Distribution of the monocarboxylate transporter MCT2 in human cerebral cortex: an immunohistochemical study. Brain Res, 2008, 1226: 61-69.
[19]
Baltan S. Can lactate serve as an energy substrate for axons in good times and in bad, in sickness and in health? Metab Brain Dis, 2015, 30(1): 25-30.
[20]
Pellerin L, Bouzier-Sore AK, Aubert A, et al. Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia, 2007, 55(12): 1251-1262.
[21]
Patet C, Suys T, Carteron L, et al. Cerebral lactate metabolism after traumatic brain injury. Curr Neurol Neurosci Rep, 2016, 16(4): 31.
[22]
Hertz L, Dienel GA. Lactate transport and transporters: general principles and functional roles in brain cells. J Neurosci Res, 2005, 79 (12): 11-18.
[23]
Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab, 2007, 27(11): 1766-1791.
[24]
Hackett MJ, Sylvain NJ, Hou H, et al. Concurrent glycogen and lactate imaging with FTIR spectroscopy to spatially localize metabolic parameters of the glial response following brain ischemia. Anal Chem, 2016. DOI:
[25]
Fan G, Wu Z, Chen L, et al. Hypoxia-ischemic encephalopathy in full-term neonate: correlation proton MR spectroscopy with MR imaging. Eur J Radiol, 2003, 45(2): 91-98.
[26]
Fujimoto S, Nabe K, Takehiro M, et al. Impaired metabolism-secretion coupling in pancreatic beta-cells: role of determinants of mitochondrial ATP production. Diabetes Res Clin Pract, 2007, 77 (Suppl 1): S2-10.
[27]
Brown AM, Ransom BR. Astrocyte glycogen and brain energy metabolism. Glia, 2007, 55(12):1263-1271.
[28]
Espinoza-Rojo M, Iturralde-Rodríguez KI, Chánez-Cárdenas ME, et al. Glucose transporters regulation on ischemic brain: possible role as therapeutic target. Cent Nerv Syst Agents Med Chem, 2010, 10(4): 317-325.
[29]
Chen C, Chen HJ, Qian LH, et al. Effect of different blood glucose levels on the expression of cerebral GLUT3 mRNA in neonatal rats with hypoxia-ischemia. Zhongguo Dang Dai Er Ke Za Zhi, 2006, 8(5): 395-401.
[30]
Zhu W, Zhong W, QI J, et al. Proton magnetic resonance spectroscopy in neonates with hypoxic-ischemic injury and its prognostic value. Transl Res, 2008, 152(5): 225-232.
[31]
Logitharajah P, Rutherford MA, Cowan FM. Hypoxic-ischemic encephalopathy in preterm infants: antecedent factors, brain imaging, and outcome. Pediatr Res, 2009, 66(2): 222-229.
[32]
Martinez-Biarge M, Diez-Sebastian J, Kapellou O, et al. Predicting motor outcome and death in term hypoxic-ischemic encephalopathy. Neurology, 2011, 76(24): 2055-2061.
[33]
Rocha-Ferreira E, Hristova M. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury. Neural plasticity, 2016: 4901014.
[34]
Provencher SW. LCModel1 & LCMgui User's Manual. 2005.
[35]
Atwood T, Payne VS, Zhao W, et al. Quantitative magnetic resonance spectroscopy reveals a potential relationship between radiation-induced changes in rat brain metabolites and cognitive impairment. Radiat Res, 2007, 168(5): 574-581.
[36]
Verma A, Saraswat VA, Radha Krishna Y, et al. In vivo (1)H magnetic resonance spectroscopy-derived metabolite variations between acute-on-chronic liver failure and acute liver failure. Liver Int, 2008. DOI:
[37]
Kyng KJ, Skajaa T, Kerrn-Jespersen S, et al. A Piglet model of neonatal hypoxic-ischemic encephalopathy. J Vis Exp, 2015, 16(99): e52454.
[38]
Zhang YF, Wang XY, Feng Guo, et al. Simultaneously changes in striatum dopaminergic and glutamatergic parameters following hypoxic-ischemic neuronal injury in newborn piglets. Eur J Paediatr Neurol, 2012, 16(3): 271-278.
[39]
Zhang YF, Wang XY, Cao L, et al. Effects of hypoxic-ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification. Nucl Medi Biology, 2011, 38(8): 1205-1212.

PREV Value of CT and MRI imaging in the diagnosis of hydrosalpinx
NEXT Study of aquaporin magnetic resonance molecular imaging in transient cerebral ischemia rat model
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn