• Journal of Biomedical Engineering Research
• /
• v.39 no.6
• /
• pp.237-242
• /
• 2018

$^{18}F$-fludeoxyglucose PET (FDG-PET) can help finding an abnormal metabolic activity in brain. In this study, we evaluated an efficiency of volume- and cortical surface-based analysis which were used to determine whether standardized uptake value ratio (SUVR) of FDG-PET was different among Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy control (HC). Each PET image was rigidly co-registered to the corresponding magnetic resonance imaging (MRI) using mutual information. All voxels of the co-registered PET images were divided by the mean FDG uptake of the cerebellum cortex which was thresholded by partial volume effect (>0.9). Also, the SUVR value of each vertex was linearly interpolated from volumetric SUVR image which was thresholded by gray matter partial volume effect (>0.1). Lobar mean values were calculated from both volume- and cortical surface-based SUVRs. Statistical analysis was conducted to compare two measures for AD, MCI and HC groups. Even though the results of volume (SUVR_vol) and cortical surface-based SUVR (SUVR_surf) analysis were not significantly different from each other, the latter would be better for detecting group differences in SUVR of PET.

• Journal of Nutrition and Health
• /
• v.34 no.7
• /
• pp.754-761
• /
• 2001

Effects of dietary fatty acids and vitamin E on antioxidant vitamin status were studied in rat brain sections. Sources of dietary fat(10t%) were safflower oil(SO) poor in $\omega$3 fatty acid and mixed oil (MO) with computer-adjustd fatty acid ratios(AA/DHA=1.4, $\omega$6/$\omega$3=6.3, P/M/S=1.0/1.5/1, AA=2.%)with (ME) and without(MO) vitamin E(500mg/kg diet). Rats were fed the three kinds of diet from 3-4 wks prior to the conception. At the age of 3 & 9wks of the 2nd generation rat, antioxidant vitamins were measured in frontal cortex(FC), corpus striatum (CS), cerebellum(CB) and hippocampus(HP) using a multiwavelength, reverse phase gradient HPLC system. The levels of antioxidant vitamins converged to the similar value in all groups at 9 wks of age. Retinol, lycopene and cryptoxanthin levels of all experimental groups were found to be the highest in hippocampus at both 3 & 9wks of age. The levels of vitamin E appeared to be higher in the order of HP>CS-CB>FC in MO & ME. Beta-carotene and retinol showed the lowest level in hippocampus of vitamin E supplemented groups, even though vitamin E level tended to be higher in other sections. It seemed that vitamin E has an inhibitory action on the uptake of beta-carotene or acts as a preferred antioxidant to beta-carotene in certain section of the brain. By improving fatty acid balance (AA/DHA = 1.4, $\omega$6/$\omega$3=6.3, P/M/S=1.0/1.5/1, AA = 2%), the levels of vitamin E, retinol, lycopene & beta=carotene tended to be higher in MO than in SO, although crytoxanthin became lower at 3wks of age. In short, dietary fatty acids and vitamin E have different influence on antioxidant vitamin status in different rat brain sections. The higher levels of antioxidant vitamins in hippocampus should be pursued further in relation to behavioral development of rats.

• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.154-161
• /
• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• The Korean Journal of Nuclear Medicine
• /
• v.35 no.1
• /
• pp.69-74
• /
• 2001

Purpose: $^{99m}Tc$-HMPAO is a radiopharmaceutical for imaging cerebral blood flow. HMPAO (RR, SS)-4.8-diaza-3,6,6,9-tetramethylundecan-2,10- dione bisoxime) has three stereoismers such as, meso-. d-, and l-HMPAO. Techentium complexes of meso-HMPAO and d,l-HMPAO are known to have different in vivo brain uptakes. In this study, enantiomers of HMPAO (d-HMPAO and l-HMPAO) were separated from d,l-HMPAO. These enantiomers were labeled with $^{99m}Tc$ and the biodistribution studies were performed in mice. Materials and Methods: An intermediate imine product was produced from 2,3-butanedione monooxime and 2,2-dimethyl-1,3-propanediamine (54% yield) and was reduced into a mixture of three isomers (35% yield). The meso-isomer was separated from d,l-mixture by repeated fractional crystallization (11 % yield). The d- and l-enantiomers were subsequently separated by co-crystallization with optical isomers of tartaric acid (25% and 5% yield. respectively). Each enantiomeric HMPAO was labeled with $^{99m}Tc$ by reacting with $SnCI_2{\cdot}2H_2O\;and\;^{99m}Tc$-pertechnetate. Biodistribution study was performed 1 hr after tail vein injection to ICR mice. Results: Radiochemical purities of each compound were over 80%. In biodistribution study. the brain uptakes of d,l- d- and l-form were 1.34, 1.12 and 1.67% ID/g, respectively. In case of l-lsomer the brain uptake was higher (1.5 fold) than d-isomer. Conclusion: We successfully purified each enantiomeric HMPAO. In biodistribution study of stereoismers of $^{99m}Tc$-HMPAO in mice, l-HMPAO may show better brain image than d,l-HMPAO which was supplied in a commercial kit.

• Journal of Biomedical Engineering Research
• /
• v.32 no.1
• /
• pp.55-60
• /
• 2011

Although sound intensity is considered as one of important factors in auditory processing, its neural mechanism in auditory neurons with limited dynamic range of firing rates is still unclear. In this study, we examined the effect of sound intensity adaptation on the change of glucose metabolism in a rat brain using [F-18] micro positron emission tomography (PET) neuroimaging technique. In the experiment, broadband white noise sound was given for 30 minutes after the [F-18]FDG injection in order to explore the functional adaptation of rat brain into the sound intensity levels. Nine rats were scanned with four different sound intensity levels: 40 dB, 60 dB, 80 dB, 100 dB sound pressure level (SPL) for four weeks. When glucose uptake during the adaptation of a high intensity sound level (100 dB SPL) was compared with that during adaptation to a low intensity level (40 dB SPL) in the experiment, the former induced a greater uptake at bilateral cochlear nucleus, superior olivary complexes and inferior colliculi in the auditory pathway. Expectedly, the metabolic activity in those areas linearly increased as the sound intensity level increased. In contrast, significant decrease interestingly occurred in the bilateral auditory cortices: The activities of auditory cortex proportionally decreased with higher sound intensities. It may reflect that the auditory cortex actively down-regulates neural activities when the sound gets louder.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.9 no.1
• /
• pp.3-8
• /
• 2023

Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.

• The Korean Journal of Nuclear Medicine
• /
• v.38 no.3
• /
• pp.268-271
• /
• 2004

A 43-year-old man was presented with persistent headache for two weeks. 72 weighted MR imaging showed high signal intensity with surrounding edema in the left frontal lobe. These findings were considered with intracranial tumor such as glioma or metastasis. Tc-99m tetrofosmin SPECT showed focal radiotracer accumulation in the left frontal lobe. The operative specimen contained cerebral infarction with organizing leptomeningeal hematoma by pathologist. Another 73-year-old man was hospitalized for chronic headache. Initial CT showed ill-defined hypodensity with mass effect in the right parietal lobe. Tc-99m tetrofosmin SPECT showed focal radiotracer uptake in the right parietal lobe. These findings were considered with low-grade glioma or infarction. Follow-up CT after 5 months showed slightly decreased in size of low density in the right parietal lobe, and cerebral infarction is more likely than others. Tc-99m tetrofosmin has been proposed as a cardiotracer of myocardial perfusion imaging and an oncotropic radiotracer. Tc-99m tetrofosmin SPECT image provides a better attractive alternative agent than T1-201 as a tumor-imaging agent, with characteristics such as high-energy flux, short half-life, favorable biodistribution, dosimetry and lower background radioactivity. We have keep in mind on the analysis of Tc-99m tetrofomin imaging when cerebral infarction is being differentiated from brain tumor.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.2
• /
• pp.147-155
• /
• 1999

Antioxidant effects of serotonin and L-DOPA on neuronal tissues were examined by studying the oxidative damages of brain synaptosomal components. The study further explored the mechanism by which they exert protective actions. Serotonin and L-DOPA (1 ${\mu}M$ to 1 mM) significantly inhibited lipid peroxidation of brain tissues by either $Fe^{2+}$ and ascorbate or t-butyl hydroperoxide in a dose dependent fashion. Protective effect of serotonin on the peroxidative actions of both systems was greater than that of L-DOPA. Protein oxidation of synaptosomes caused by $Fe^{2+}$ and ascorbate was attenuated by serotonin and L-DOPA. Protein oxidation more sensitively responded to L-DOPA rather than serotonin. Serotonin and L-DOPA (100 ${\mu}M$) decreased effectively the oxidation of synaptosomal sulfhydryl groups caused by $Fe^{2+}$ and ascorbate. The production of hydroxyl radical caused by either $Fe^{3+},$ EDTA, H_2O_2$ and ascorbate or xanthine and xanthine oxidase was significantly decreased by serotonin and L-DOPA (1 mM). Equal concentrations of serotonin and L-DOPA restored synaptosomal $Ca^{2+}$ uptake decreased by $Fe^{2+}$ and ascorbate, which is responsible for SOD and catalase. Protective effects of serotonin and L-DOPA on brain synaptosomes may be attributed to their removing action on reactive oxidants, hydroxyl radicals and probably iron-oxygen complex, without chelating action on iron.

• Journal of Pharmaceutical Investigation
• /
• v.30 no.2
• /
• pp.99-105
• /
• 2000

This study compared the permeability of $[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ through the blood-brain barrier (BBB) in mice and rats with common carotid artery perfusion (CCAP) method that modified internal carotid artery perfusion (ICAP) method. External carotid artery (ECA) was cannulated with coagulating pterygopalatine artery (PPA) in ICAP method, while CCA was cannulated without coagulating PPA in CCAP method. Also, for evaluation of BBB permeability of drugs in mice and rats, we used intravenous injection technique. The results of CCAP method in mice at a perfusion flow-rate of 2 ml/min, the brian volume of distribution $(V_D)$ of $[^{14}C]sucrose,\;[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ were similar to the result of ICAP method in rats at perfusion flow rate of 4 ml/min. The area under the plasma concentration-time curve and brain uptake of $[^3H]taurine$ by intravenous injection technique, were $65.5{\pm}9.7%ID^*min/ml\;and\;0.515{\pm}0.093%ID/g$, respectively, in mice, and the corresponding values were $8.00{\pm}0.03%ID^*min/ml\;and\;0.052{\pm}0.003%ID/g$ in rats. But the BBB permeability surface-area product of $[^3H]taurine$ was similar between mice and rats. In conclusion, the CCAP method in mice was simple, fast and comparable to ICAP method in rats for drug permeability through the BBB.

• Korean Journal of Exercise Nutrition
• /
• v.24 no.4
• /
• pp.15-23
• /
• 2020

[Purpose] Lactate is a principal energy substrate for the brain during exercise. A single bout of high-intensity interval exercise (HIIE) can increase the blood lactate level, brain lactate uptake, and executive function (EF). However, repeated HIIE can attenuate exercise-induced increases in lactate level and EF. The lactate levels in the brain and blood are reported to be correlated with exercise-enhanced EF. However, research is yet to explain the cause-and-effect relationship between lactate and EF. This study examined whether lactate consumption improves the attenuated exercise-enhanced EF caused by repeated HIIE. [Methods] Eleven healthy men performed two sets of HIIE, and after each set, 30 min were given for rest and examination. In the 2^nd set, the subjects consumed experimental beverages containing (n = 6) and not containing (n = 5) lactate. Blood, cardiovascular, and psychological variables were measured, and EF was evaluated by the computerized color-word Stroop test. [Results] The lactate group had a higher EF (P < 0.05) and tended to have a higher blood lactate level (P = 0.082) than the control group in the 2^nd set of HIIE. Moreover, blood lactate concentration was correlated with the interference score (i.e., reverse score of EF) (r = -0.394; P < 0.05). [Conclusion] Our results suggest that the attenuated exercise-enhanced EF after repeated HIIE can be improved through lactate consumption. However, the role of lactate needs to be elucidated in future studies, as it can be used for improving athletes' performance and also in cognitive decline-related clinical studies.