Glucose Metabolic Alteration of Cerebral Cortical Subareas in Rats with Renal Ischemia/Reperfusion Based on Small-Animal Positron Emission Tomography

Abstract

Objective

To investigate glucose metabolic alterations in cerebral cortical subareas using ¹⁸F-labeled glucose derivative fluorodeoxyglucose (FDG) micro-positron emission tomography (PET) scanning in a rat renal ischemia/reperfusion (RIR) model.

Methods

Small-animal PET imaging in vivo was performed with ¹⁸F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.

Results

We found that the average standardized uptake value (SUV_average) of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group (P<0.05). We also found that glucose uptake in different cortical subregions including the left auditory cortex, right medial prefrontal cortex, right para cortex, left retrosplenial cortex, right retrosplenial cortex, and right visual cortex was significantly increased in the RIR group (P<0.05), but there was no significant difference in the SUV_average of right auditory cortex, left medial prefrontal cortex, left para cortex, and left visual cortex between the two groups.

Conclusion

The ¹⁸F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.

Keywords

renal ischemia/reperfusion / cerebral cortex / glucose uptake / ¹⁸F-fluorodeoxyglucose / positron emission tomography

References

[1] XiangHB, ZhuWZ, GuanXH, et al.. Possible mechanism of deep brain stimulation for pedunculopontine nucleusinduced urinary incontinence: a virally mediated transsynaptic tracing study in a transgenic mouse model. Acta Neurochir (Wien), 2013, 155(9): 1667-1669

[2] XiangHB, ZhuWZ, BuHL, et al.. Possible mechanism of subthalamic nucleus stimulationinduced acute renal failure: a virally mediated transsynaptic tracing study in transgenic mouse model. Mov Disord, 2013, 28(14): 2037-2038

[3] LiuC, YeDW, GuanXH, et al.. Stimulation of the pedunculopontine tegmental nucleus may affect renal function by melanocortinergic signaling. Med Hypotheses, 2013, 81(1): 114-116

[4] YeDW, LiRC, WuW, et al.. Role of spinal cord in regulating mouse kidney: a virally mediated transsynaptic tracing study. Urology, 2012, 79(3): 745 e1-4

[5] YeD, GuoQ, FengJ, et al.. Laterodorsal tegmentum and pedunculopontine tegmental nucleus circuits regulate renal functions: Neuroanatomical evidence in mice models. J Huazhong Univ Sci Technolog Med Sci, 2012, 32(2): 216-220

[6] LiuTT, LiuBW, HeZG, et al.. Delineation of the central melanocortin circuitry controlling the kidneys by a virally mediated transsynaptic tracing study in transgenic mouse model. Oncotarget, 2016, 7(43): 69256-69266

[7] FengM, XiangB, FanL, et al.. Interrogating autonomic peripheral nervous system neurons with viruses - A literature review. J Neurosci Methods, 2020, 346: 108958

[8] FanL, XiangB, XiongJ, et al.. Use of viruses for interrogating viscera-specific projections in central nervous system. J Neurosci Methods, 2020, 341: 108757

[9] ZhouW, BaoW, JiangD, et al.. [(18)F]-GE-179 positron emission tomography (PET) tracer for N-methyl-daspartate receptors: One-pot synthesis and preliminary micro-PET study in a rat model of MCAO. Nucl Med Biol, 2018, 61: 45-55

[10] BonaventuraJ, EldridgeMAG, HuF, et al.. Highpotency ligands for DREADD imaging and activation in rodents and monkeys. Nat Commun, 2019, 10: 4627

[11] OgawaM, WatabeH, TeramotoN, et al.. Understanding of cerebral energy metabolism by dynamic living brain slice imaging system with [18F]FDG. Neurosci Res, 2005, 52(4): 357-361

[12] PanXC, LiZX, WuDZ, et al.. Mapping Changes of Whole Brain Blood Flow in Rats with Myocardial Ischemia/Reperfusion Injury Assessed by Positron Emission Tomography. Curr Med Sci, 2019, 39(4): 653-657

[13] MittraES, KoglinN, MosciC, et al.. Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)- L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies. PLoS One, 2016, 11(2): e0148628

[14] SchoffelenR, SharkeyRM, GoldenbergDM, et al.. Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts. Mol Cancer Ther, 2010, 9(4): 1019-1027

[15] WangH, TangG, HuK, et al.. Comparison of three (1) (8)F-labeled carboxylic acids with (1)(8)F-FDG of the differentiation tumor from inflammation in model mice. BMC Med Imaging, 2016, 16: 2

[16] TianJL, CuiBP. Mixed epithelial and stromal tumor of the kidney on 18F-FDG PET/CT in a 21-year-old female. Saudi Med J, 2019, 40(5): 499-502

[17] DumRP, StrickPL. Transneuronal tracing with neurotropic viruses reveals network macroarchitecture. Curr Opin Neurobiol, 2013, 23(2): 245-249

[18] SongN, ZhangT, XuX, et al.. miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation. Front Physiol, 2018, 9: 790

[19] Raup-KonsavageWM, WangY, WangWW, et al.. Neutrophil peptidyl arginine deiminase-4 has a pivotal role in ischemia/reperfusion-induced acute kidney injury. Kidney Int., 2018, 93(2): 365-374

[20] SinghAP, SinghN, PathakD, et al.. Estradiol attenuates ischemia reperfusion-induced acute kidney injury through PPAR-gamma stimulated eNOS activation in rats. Mol Cell Biochem, 2019, 453(1–2): 1-9

[21] D’AscenzoN, GaoM, AntonecchiaE, et al.. New Digital Plug and Imaging Sensor for a Proton Therapy Monitoring System Based on Positron Emission Tomography. Sensors (Basel), 2018, 18(9): 3006

[22] XiD, LiuX, ZengC, et al.. Modularized compact positron emission tomography detector for rapid system development. J Med Imaging (Bellingham), 2017, 4(1): 011006

[23] LiuQQ, LiuH, HeZG, et al.. Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats. Oncotarget, 2017, 8(32): 53 465-53 481

[24] Di PaolaR, GenoveseT, ImpellizzeriD, et al.. The renal injury and inflammation caused by ischemiareperfusion are reduced by genetic inhibition of TNFalphaR1: a comparison with infliximab treatment. Eur J Pharmacol, 2013, 700(1–3): 134-146

[25] YamamotoS, HagiwaraS, HidakaS, et al.. The antioxidant EPC-K1 attenuates renal ischemia-reperfusion injury in a rat model. Am J Nephrol, 2011, 33(6): 485-490

[26] FeltesCM, HassounHT, LieML, et al.. Pulmonary endothelial cell activation during experimental acute kidney injury. Shock, 2011, 36(2): 170-176

[27] SlyDJ, ColvillL, McKinleyMJ, et al.. Identification of neural projections from the forebrain to the kidney, using the virus pseudorabies. J Auton Nerv Syst, 1999, 77(2–3): 73-82

[28] CanoG, CardJP, SvedAF. Dual viral transneuronal tracing of central autonomic circuits involved in the innervation of the two kidneys in rat. J Comp Neurol, 2004, 471(4): 462-481

[29] AttwellD, LaughlinSB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab, 2001, 21(10): 1133-1145

[30] HeoJH, LeeSR, LeeST, et al.. Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys. J Alzheimers Dis, 2011, 25(3): 517-523

[31] ZhangHJ, MitchellS, FangYH, et al.. Assessment of Brain Glucose Metabolism Following Cardiac Arrest by [(18)F]FDG Positron Emission Tomography. Neurocrit Care, 2020, 34(1): 64-72

[32] BuschiazzoA, CossuV, BaucknehtM, et al.. Effect of starvation on brain glucose metabolism and (18)F-2- fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study. EJNMMI Res, 2018, 8(1): 44

[33] LevinthalDJ, StrickPL. The motor cortex communicates with the kidney. J Neurosci, 2012, 32(19): 6726-6731

[34] DumRP, LevinthalDJ, StrickPL. The mind-body problem: Circuits that link the cerebral cortex to the adrenal medulla. Proc Natl Acad Sci USA, 2019, 116(52): 26321-26328

[35] EustonDR, GruberAJ, McNaughtonBL. The Role of Medial Prefrontal Cortex in Memory and Decision Making. Neuron, 2012, 76(6): 1057-1070

[36] JahnA, NeeDE, AlexanderWH, et al.. Distinct Regions within Medial Prefrontal Cortex Process Pain and Cognition. J Neurosci, 2016, 36(49): 12385-12392

[37] CsanovaA, HlavacovaN, HasiecM, et al.. beta3- Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats. Stress, 2017, 20(3): 294-302

[38] GrzelkaK, GawlakM, CzarzastaK, et al.. Effects of beta3-adrenergic receptor stimulation on the resting holding current of medial prefrontal cortex pyramidal neurons in young rats. Neurosci Lett, 2019, 698: 192-197

[39] WangH, HuangB, WangW, et al.. High urea induces depression and LTP impairment through mTOR signalling suppression caused by carbamylation. EBioMedicine, 2019, 48: 478-490

[40] ZhangXD, WenJQ, XuQ, et al.. Altered long- and short-range functional connectivity in the patients with end-stage renal disease: a resting-state functional MRI study. Metab Brain Dis, 2015, 30(5): 1175-1186

[41] DongJ, MaX, LinW, et al.. Aberrant cortical thickness in neurologically asymptomatic patients with end-stage renal disease. Neuropsychiatr Dis Treat, 2018, 14: 1929-1939

[42] LuH, GuZ, XingW, et al.. Alterations of default mode functional connectivity in individuals with end-stage renal disease and mild cognitive impairment. BMC Nephrol, 2019, 20(1): 246