The hypothalamus for whole-body physiology: from metabolism to aging

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.

Exploration of mechanism of "simultaneous treatment of brain and heart" of Naoxintong Capsules based on Toll-like receptor signaling pathway / 中国中药杂志

This study aims to explore the mechanism of "simultaneous treatment of the brain and the heart" of Naoxintong Capsules(NXT) under cerebral ischemia based on Toll-like receptor(TLR) signaling pathway.Male SD rats were randomized into sham operation group, model group, NXT group, and positive drug group.Middle cerebral artery occlusion(MCAO) model rats were used in model group, NXT group, and positive drug group, respectively.Neurological function was scored with the Bederson scale, and brain infarct rate was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining.Brain edema was detected with wet-dry weight method.Hematoxylin-eosin(HE) staining and TdT-mediated dUTP nick-end labeling(TUNEL) staining were used to observe and count apoptotic cardiocytes.In addition, serum myocardial enzymes were measured.The expression of 8 TLR signaling pathway-related proteins interferon-α(IFN-α), interferon regulatory factor-3(IRF3), interferon regulatory factor-7(IRF7), TLR2, TLR4, TLR7, TLR9, and tumor necrosis factor-α(TNF-α) in the cerebral cortex and heart of rats was detected by Western blot. Brain infarct rate, neurological function score, and brain water content in NXT group decreased significantly compared with those in the model group. At the same time, the reduction in apoptosis rate of cardiocytes and the content of serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), creatine kinase(CK), and lactate dehydrogenase(LDH) were decreased in the NXT group.Systems pharmacological results and previous research showed that TLR signaling pathway played an important role in immune inflammatory response.The study of TLR signaling pathway and related proteins is helpful to elucidate the mechanism of "simultaneous treatment of the brain and the heart". Western blot results showed that NXT significantly inhibited the expression of IRF3, IRF7, TLR2, TLR7, and TNF-α in cerebral cortex and heart under cerebral ischemia.Cerebral ischemia influences cardiac functions, and TLR signaling pathway is one of the pathways for "simultaneous treatment of the brain and the heart" of NXT.

Global Profiles of Acetylated Proteins in Brains of Scrapie Agents 139A- and ME7-Infected Mice Collected at Mid-Early, Mid-Late, and Terminal Stages / 生物医学与环境科学（英文）

OBJECTIVE@#To describe the global profiles of acetylated proteins in the brains of scrapie agents 139A- and ME7-infected mice collected at mid-early, mid-late, and terminal stages.@*METHODS@#The acetylated proteins from the cortex regions of scrapie agent (139A- and ME7)-infected mice collected at mid-early (80 days postinfection, dpi), mid-late (120 dpi), and terminal (180 dpi) stages were extracted, and the global profiles of brain acetylated proteins were assayed with proteomic mass spectrometry. The proteins in the infected mice showing 1.5-fold higher or lower levels than that of age-matched normal controls were considered as differentially expressed acetylated peptides (DEAPs).@*RESULTS@#A total of 118, 42, and 51 DEAPs were found in the brains of 139A-80, 139A-120, and 139A-180 dpi mice, respectively. Meanwhile, 390, 227, and 75 DEAPs were detected in the brains of ME7-80, ME7-120, and ME7-180 dpi mice, respectively. The overwhelming majority of DEAPs in the mid-early stage were down-regulated, and more portions of DEAPs in the mid-late and late stages were up-regulated. Approximately 22.1% (328/1,485) of acetylated peptides mapped to 74 different proteins were mitochondrial associated. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 39 (80 dpi), 13 (120 dpi), and 10 (180 dpi) significantly changed pathways in 139A-infected mice. Meanwhile, 55, 25, and 18 significantly changed pathways were observed in the 80, 120, and 180 dpi samples of 139A- and ME7-infected mice ( P < 0.05), respectively. Six pathways were commonly involved in all tested samples. Moreover, many steps in the citrate cycle (tricarboxylic acid cycle) were affected, represented by down-regulated acetylation for relevant enzymes in the mid-early stage and up-regulated acetylation in the mid-late and late stages.@*CONCLUSION@#Our data here illustrated the changes in the global profiles for brain acetylated proteins during prion infection, showing remarkably inhibited acetylation in the early stage and relatively enhanced acetylation in the late stage.

Effect of Biantie pretreatment on serum level of PHD2/HIF-1α and brain tissue damage in rats during acute hypobaric hypoxia exposure / 中国针灸

OBJECTIVE@#To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude.@*METHODS@#Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR.@*RESULTS@#Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05).@*CONCLUSION@#Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.

Expert Consensus on the Treatment of Antiangiogenic Agents for Radiation Brain Necrosis / 中国肺癌杂志

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Discovery and confirmation of protein action site AK1 of ginsenosides in brain based on DARTS technology / 中国中药杂志

This study aims to explore the targets of ginsenosides in brain based on drug affinity responsive target stability(DARTS) technology. Specifically, DARTS technology was combined with label-free liquid chromatography tandem mass spectrometry(LC-MS) to screen out the proteins in the brain that might interact with ginsenosides. Based on the screening results, adenylate kinase 1(AK1) was selected for further confirmation. First, the His-AK1 fusion protein was yielded successively through the construction of recombinant prokaryotic expression vector, expression of target protein, and purification of the fusion protein. Biolayer interferometry(BLI) was employed to detect the direct interaction of Rg_1, Re, Rb_1, Rd, Rh_2, F1, Rh_1, compound K(CK), 25-OH-PPD, protopanaxa-diol(PPD), and protopanaxatriol(PPT) with AK1, thereby screening the ginsenoside monomer or sapogenin that had strong direct interaction with the suspected target protein AK1. Then, the BLI was used to further determine the kinetic parameters for the binding of PPD(strongest interaction with AK1) to His-AK1 fusion protein. Finally, molecular docking technology was applied to analyze the binding properties between the two. With DARTS and LC-MS, multiple differential proteins were screened out, and AK1 was selected based on previous research for target verification. Fusion protein His-AK1 was obtained by prokaryotic expression, and the response(nm) of Re, Rg_1, Rd, Rb_1, Rh_1, Rh_2, F1, PPT, PPD, 25-OH-PPD, and CK with His-AK1 was respectively 0.003 1, 0.001 9, 0.042 8, 0.022 2, 0.013 4, 0.037 3, 0.013 9, 0.030 7, 0.140 2, 0.016 0, and 0.040 8. The K_(on), K_(off), and K_D values of PPD and His-AK1 were determined by the BLI as 1.22×10~2 mol~(-1)·L·s~(-1), 1.04×10~(-2) s~(-1), 8.52×10~(-5) mol·L~(-1). According to the molecular docking result, PPD bound to AK1 with the absolute value of the docking score of 3.438, and hydrogen bonds mainly formed between the two. Thus, AK1 is one of the protein action sites of ginsenosides in the brain. The direct interaction between ginsenoside metabolite PPD and AK1 is the strongest.

Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebral β-amyloid deposition and brain atrophy / 中华医学杂志(英文版)

BACKGROUND@#Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.@*METHODS@#We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.@*RESULTS@#The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.@*CONCLUSION@#Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.

Blood-cerebrospinal fluid (CSF) barrier dysfunction means reduced CSF flow not barrier leakage - conclusions from CSF protein data / Disfunção da barreira hemato-liquórica significa redução do fluxo de líquido cefalorraquidiano, e não quebra de barreira - conclusões a partir de estudos sobre as proteínas do LCR

ABSTRACT Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause. Results: Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers. Serum protein concentrations in lumbar CSF increase with hyperbolic functions, but the levels of proteins that do not pass the barrier remain constant (brain proteins) or increase linearly (leptomeningal proteins). All CSF protein dynamics above and below a lumbar blockade can also be explained, independent of their barrier passage, by a reduced caudally directed flow. Local accumulation of gadolinium in multiple sclerosis (MS) is now understood as due to reduced bulk flow elimination by interstitial fluid (ISF). Nonlinear change of the steady state in barrier dysfunction and along normal rostro-caudal gradients supports the diffusion/flow model and contradicts obstructions of diffusion pathways. Regardless of the cause of the disease, pathophysiological flow blockages are found in bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS and experimental allergic encephalomyelitis. In humans, the fortyfold higher albumin concentrations in early fetal development decrease later with maturation of the arachnoid villi, i.e., with beginning CSF outflow, which contradicts a relevant outflow to the lymphatic system. Respiration- and heartbeat-dependent oscillations do not disturb net direction of CSF flow. Conclusion: Blood-CSF and blood-brain barrier dysfunctions are an expression of reduced CSF or ISF flow rate.

RESUMO Introdução: Concentrações aumentadas de proteínas séricas no líquido cefalorraquidiano são interpretadas como disfunção da barreira (hemato-liquórica) sanguínea do LCR. Interpretações frequentemente usadas, como vazamento de barreira (quebra ou rompimento de barreira), rompimento ou quebra, contradiz os dados de proteína do LCR, que sugerem uma taxa de fluxo reduzida do LCR como a causa. Resultados: Mesmo as disfunções de barreira mais graves não alteram a seletividade dependente do tamanho molecular nem a variação interindividual da transferência de proteína através de barreiras. As concentrações de proteínas séricas no LCR lombar aumentam com as funções hiperbólicas, mas as proteínas que não passam a barreira permanecem constantes (proteínas do cérebro) ou aumentam linearmente (proteínas leptomeningeais). Toda a dinâmica das proteínas do LCR acima e abaixo de um bloqueio lombar também pode ser explicada, independente de sua passagem pela barreira, por um fluxo caudal reduzido. O acúmulo local de gadolínio na esclerose múltipla (EM) é agora entendido como decorrente da redução da eliminação do bulk flow pelo fluido intersticial (FIS). A mudança não linear do estado estacionário na disfunção da barreira e ao longo dos gradientes rostro-caudais normais apoia o modelo de difusão/fluxo e contradiz as obstruções das vias de difusão. Independentemente da causa da doença, os bloqueios fisiopatológicos do fluxo são encontrados na meningite bacteriana, leucemia, carcinomatose meníngea, síndrome de Guillain-Barré, EM e encefalomielite alérgica experimental. Em humanos, as concentrações de albumina quarenta vezes mais altas no desenvolvimento fetal inicial diminuem tarde com a maturação das vilosidades aracnoides, isto é, com o início do fluxo de LCR, o que contradiz um fluxo relevante para o sistema linfático. As oscilações dependentes da respiração e do batimento cardíaco não perturbam a direção do fluxo do LCR. Conclusão: As disfunções das barreiras hemato-liquórica e hemato-encefálica são uma expressão da redução da taxa de fluxo do LCR ou FIS.

Protective effects of active compounds from on heart and brain of mice at simulated high altitude / 浙江大学学报·医学版

To investigate the active compounds from on the heart and brain of mice at simulated high altitude.Fifty healthy male adult BALB/c mice were randomly divided into normal control group, hypoxic model group, acetazolamide group, petroleum ether extract of (PESI) group and octacosan group with 10 mice in each group. Acetazolamide group, PESI group and octacosan group were treated with acetazolamide PESI (200 mg/kg) or octacosan by single tail vein injection, respectively. Except normal control group, the mice were exposed to a simulated high altitude of for in an animal decompression chamber. After the mice were sacrificed by cervical dislocation, the heart and brain were histologically observed by HE staining; superoxide dismutase (SOD) activity, total anti-oxidant capacity (T-AOC) and the content of malondialdehyde (MDA) in plasma, heart and brain tissues were detected by WST-1 method, ABTS method and TBA method, respectively; lactic acid and lactate dehydrogenase (LDH) activity in plasma, heart and brain tissues were detected by colorimetric method and microwell plate method, respectively; ATP content and ATPase activity in heart and brain tissues were detected by colorimetric method. PESI and octacosane significantly attenuated the pathological damages of heart and brain tissue at simulated high altitude; increased SOD activity, T-AOC and LDH activity, and decreased the contents of MDA and lactic acid in plasma, heart and brain tissues; increased the content of ATP in heart and brain tissues; increased the activities of Na-K ATPase, Mg ATPase, Ca ATPase and Ca-Mg ATPase in myocardial tissue; and increased the activities of Mg ATPase, Ca-Mg ATPase in brain tissue. PESI and octacosan exert anti-hypoxic activity by improving the antioxidant capacity, reducing the free radical levels, promoting the anaerobic fermentation, and alleviating the energy deficiency and metabolic disorders caused by hypoxia in mice.

Aging and low-intensity exercise change oxidative biomarkers in brain regions and radiographic measures of femur of Wistar rats

We investigated changes in oxidative biomarkers in brain regions such as brainstem, cerebellum, and cerebral cortex of 3-, 6-, 18-, 24-, and 30-month-old rats. We also assessed the effects of low-intensity exercise on these biomarkers in these regions of 6-, 18-, and 24-month-old rats that started exercise on a treadmill at 3, 15, and 21 months of age, respectively. Radiographic images of the femur were taken for all rats. A total of 25 rats (age: twelve 6-, ten 18-, ten 24-, and three 30-month-old rats) were used. Lipid hydroperoxide levels increased in cerebellum at 18 months. Total antioxidant activity exhibited lowest values in brainstem at 3 months. Superoxide dismutase activity did not exhibit significant changes during aging. Total thiol content exhibited lowest values in brain regions of 24- and 30-month-old rats. Exercise reduced total thiol content in brainstem at 6 months, but no change occurred in other regions and other ages. Femur increased its length and width and cortical thickness with advancing age. No change occurred in medullary width. Radiolucency increased and sclerosis was found in cortical and medullary bone with advancing age. Exercise reduced radiolucency and medullary sclerosis. Therefore, aging differentially changed oxidative biomarkers in different brain regions and radiographic measures of the femur. Low-intensity exercise only ameliorated some radiographic measurements of femur. Since the present study possessed limitations (small number of rats per group), a beneficial effect of regular low-intensity exercise on oxidative markers in brain cannot be ruled out.

Role of microglial pyroptosis in hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To investigate the role of microglial pyroptosis in hypoxic-ischemic brain damage.@*METHODS@#An oxygen-glucose deprivation/reoxygenation (OGD/R) model of rat microglial cells were cultured in vitro. Western blot was used to measure the expression of the pyroptosis-related proteins caspase-1, interleukin-1β (IL-1β), and N-terminal gasdermin D (GSDMD-N) at 0, 1, 3, 6, 12, and 24 hours after OGD/R. After the microglial cells were transfected with lentivirus-mediated silenced gasdermin D (GSDMD), immunofluorescence assay and Western blot were used to measure the transfection rate of GSDMD. Microglial cell lines were divided into three groups: normal control, negative control, and LV-sh_GSDMD (lentivirus-mediated GSDMD silencing). CCK-8 assay and LDH kit were used to observe the effect of GSDMD silencing on the viability and toxicity of microglial cells at 24 hours after OGD/R. Western blot was used to observe the effect of GSDMD silencing on the levels of caspase-1, GSDMD-N, and IL-1β in the microglial cells at 24 hours after OGD/R.@*RESULTS@#The expression levels of the pyroptosis-related proteins caspase-1, GSDMD-N, and IL-1β in microglial cells were upregulated since 0 hour after OGD/R and reached the peak levels at 24 hours. A microglial cell model of lentivirus-mediated GSDMD silencing was successfully constructed. At 24 hours after OGD/R, compared with the normal control group, the GSDMD silencing group had a significant increase in the cell viability and a significant reduction in the cytotoxicity (P<0.05), as well as significant reductions in the protein expression levels of caspase-1, GSDMD-N, and IL-1β in microglial cells (P<0.05).@*CONCLUSIONS@#Lentivirus silencing of the key substrate protein for pyroptosis GSDMD can alleviate hypoxic-ischemic brain damage, suggesting that microglial pyroptosis aggravates hypoxic-ischemic brain damage.

Effects of oxidative stress on liver, brain and spinal cord of rats using L-NAME and treated with hydroxyurea. A model of sickle cell complication

Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

Effects of growth hormone in the central nervous system

ABSTRACT Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch Endocrinol Metab. 2019;63(6):549-56

Comparison of different quantification methods for 18F-fluorodeoxyglucose-positron emission tomography studies in rat brains

OBJECTIVES: This study aimed to evaluate several methods to estimate glucose consumption in the male Wister rat brain as measured by PET. METHODS: Fourteen male Wistar normoglycemic rats were studied. The input function consisted of seventeen blood samples drawn manually from the femoral artery. Glucose uptake values were calculated using the input function resulting from the arterial blood samples and the tissue time-activity curve derived from the PET images. The estimated glucose consumption rate (Ki) based on the 2-tissue compartment model (2TCM) served as the standard for comparisons with the values calculated by the Patlak analysis and with the fractional uptake rate (FUR), standardized uptake value (SUV) and glucose corrected SUV (SUVglu). RESULTS: No significant difference between the standard Ki and the Patlak Ki was observed. The standard Ki was also found to have strong correlations and concordance with the Ki value estimated by the Patlak analysis. The FUR method presented an excellent correlation with the Ki value obtained by the 2TCM/Patlak analyses, in contrast to the SUV or SUVglu. CONCLUSIONS: From a methodological point of view, the present findings confirm the theoretical limitations of the cerebral SUV and SUVglu as a substitute for Ki in the estimation of glucose consumption in the brain. Our data suggest that the FUR is the surrogate to Ki.

Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice

High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes.

Effects of cerebral oxygen changes during coronary bypass surgery on postoperative cognitive dysfunction in elderly patients: a pilot study / Efeitos das alterações no oxigênio cerebral durante cirurgia de revascularização do miocárdio sobre a disfunção cognitiva no pós-operatório em pacientes idosos: estudo piloto

Abstract Background and objectives: Postoperative cognitive dysfunction is common after cardiac surgery. Adequate cerebral perfusion is essential and near infrared spectroscopy (NIRS) can measure cerebral oxygenation. Aim of this study is to compare incidence of early and late postoperative cognitive dysfunction in elderly patients treated with conventional or near infrared spectroscopy monitoring. Methods: Patients undergoing coronary surgery above 60 years, were included and randomized to 2 groups; control and NIRS groups. Peroperative management was NIRS guided in GN; and with conventional approach in control group. Test battery was performed before surgery, at first week and 3rd month postoperatively. The battery comprised clock drawing, memory, word list generation, digit spam and visuospatial skills subtests. Postoperative cognitive dysfunction was defined as drop of 1 SD (standard deviation) from baseline on two or more tests. Mann-Whitney U test was used for comparison of quantitative measurements; Chi-square exact test to compare quantitative data. Results: Twenty-one patients in control group and 19 in NIRS group completed study. Demographic and operative data were similar. At first week postoperative cognitive dysfunction were present in 9 (45%) and 7 (41%) of patients in control group and NIRS group respectively. At third month 10 patients (50%) were assessed as postoperative cognitive dysfunction; incidence was 4 (24%) in NIRS group (p:0.055). Early and late postoperative cognitive dysfunction group had significantly longer ICU stay (1.74 + 0.56 vs. 2.94 + 0.95; p < 0.001; 1.91 + 0.7 vs. 2.79 + 1.05; p < 0.01) and longer hospital stay (9.19 + 2.8 vs. 11.88 + 1.7; p < 0.01; 9.48 + 2.6 vs. 11.36 + 2.4; p < 0.05). Conclusion: In this pilot study conventional monitoring and near infrared spectroscopy resulted in similar rates of early postoperative cognitive dysfunction. Late cognitive dysfunction tended to ameliorate with near infrared spectroscopy. Early and late cognitive declines were associated with prolonged ICU and hospital stays.

Resumo Justificativa e objetivos: A disfunção cognitiva no pós-operatório é comum após cirurgia cardíaca. A perfusão cerebral adequada é essencial e a espectroscopia no infravermelho próximo (NIRS) pode medir a oxigenação cerebral. O objetivo deste estudo foi comparar a incidência de disfunção cognitiva no pós-operatório, precoce e tardio, em pacientes idosos tratados com monitoração convencional ou espectroscopia no infravermelho próximo. Métodos: Os pacientes submetidos à cirurgia coronariana, acima de 60 anos, foram incluídos e randomicamente alocados em dois grupos: grupo controle e grupo NIRS. O manejo dos pacientes no período perioperatório foi feito com NIRS no grupo NH e com abordagem convencional no grupo controle A bateria de testes foi feita antes da cirurgia, na primeira semana e no terceiro mês de pós-operatório. A bateria incluiu o desenho do relógio, a memória, a geração de uma lista de palavras, a sequência de dígitos e subtestes que exigem habilidades visuoespaciais.Disfunção cognitiva no pós-operatório foi definida como queda de um DP (desvio-padrão) da fase basal em dois ou mais testes. O teste U de Mann Whitney foi usado para comparação de medidas quantitativa e o teste exato do qui-quadrado para comparar dados quantitativos. Resultados: Vinte e um pacientes do grupo controle e 19 do grupo NIRS concluíram o estudo. Os dados demográficos e operacionais foram semelhantes. Na primeira semana, nove pacientes (45%) do GC e sete pacientes (41%) do grupo NIRS apresentaram disfunção cognitiva no pós-operatório. No terceiro mês, 10 pacientes (50%) foram avaliados como disfunção cognitiva no pós-operatório; a incidência foi de quatro (24%) no grupo NIRS (p = 0,055). O grupo que apresentou disfunção cognitiva no pós-operatório precoce e tardio teve uma permanência significativamente maior na UTI (1,74 + 0,56 vs. 2,94 + 0,95; p < 0,001; 1,91 + 0,7 vs. 2,79 + 1,05; p < 0,01) e permanência hospitalar mais longa (9,19 + 2,8 vs. 11,88 + 1,7; p < 0,01; 9,48 + 2,6 vs. 11,36 + 2,4; p < 0,05). Conclusão: Neste estudo piloto, a monitoração convencional e a espectroscopia no infravermelho próximo resultaram em taxas semelhantes de disfunção cognitiva no pós-operatório precoce. A disfunção cognitiva tardia tende a melhorar com espectroscopia no infravermelho próximo. Os declínios cognitivos precoces e tardios foram associados a internações prolongadas tanto em UTI quanto hospitalares.

Does Parkinson's disease start in the gut? / A doença de Parkinson começa no intestino?

ABSTRACT Current understanding of the pathophysiology of Parkinson's disease suggests a key role of the accumulation of alpha-synuclein in the pathogenesis. This critical review highlights major landmarks, hypotheses and controversies about the origin and progression of synucleinopathy in Parkinson's disease, leading to an updated review of evidence suggesting the enteric nervous system might be the starting point for the whole process. Although accumulating and compelling evidence favors this theory, the remaining knowledge gaps are important points for future studies.

RESUMO O atual entendimento sobre a fisiopatologia da doença de Parkinson (DP) sugere um papel central do acúmulo de alfa-sinucleína na patogenia da DP Esta revisão crítica revisita marcos, teorias e controvérsias a respeito da origem e progressão da sinucleinopatia, apresentando uma atualização das principais evidências sugerindo que o sistema nervoso entérico seria o local inicial deste processo. Apesar das evidências a favor desta teoria serem crescentes e instigantes, as lacunas de conhecimento a este respeito são importantes pontos para estudos futuros.

Effect of different commercial fat sources on brain, liver and blood lipid profiles of rats in growth phase

Abstract Purpose: To investigate the fatty acid content of different fat sources and evaluate the effect of them on plasma and hepatic lipids and on the fatty acid profile of the brain tissue of Wistar rats. Methods: Thirty male albino Wistar rats received for 59 days, the following diets: diet added of margarine with low content of polyunsaturated fatty acids (PUFA); diet added of margarine with high content of PUFA; diet added of butter; diet added of hydrogenated vegetable fat; diet added of soybean oil. Fatty acid profile of the lipid sources, blood and hepatic lipids fractions and fatty acid profile of the brain tissue were determined. Results: Margarine consumption of provided different responses as to concentrations of blood and hepatic lipid fractions. Intake of butter and hydrogenated increased LDL-c/HDL-c ratio, being the steepest increase promoted by hydrogenated vegetable fat, which also raised LDL-c levels expressively. All fats used in the treatments reduced the cerebral concentration of docosahexaenoic acid when compared to soybean oil (control). Conclusion: The different fat sources commonly consumed by population provided different responses in vivo. This is particularly relevant considering the role of these lipids in the incidence and prevention of cardiovascular diseases.

The prognostic value of cerebral oxygen saturation measurement for assessing prognosis after cardiopulmonary resuscitation / O valor da medida da saturação cerebral de oxigênio para avaliar o prognóstico após ressuscitação cardiopulmonar

Abstract Background: Despite new improvements on cardiopulmonary resuscitation (CPR), brain damage is very often after resuscitation. Objective: To assess the prognostic value of cerebral oxygen saturation measurement (rSO2) for assessing prognosis on patients after cardiopulmonary resuscitation. Design: Retrospective analysis. Measurements and results: We analyzed 25 post-CPR patients (12 female and 13 male). All the patients were cooled to a target temperature of 33-34 °C. The Glascow Coma Scale (GCS), Corneal Reflexes (CR), Pupillary Reflexes (PR), arterial Base Excess (BE) and rSO2 measurements were taken on admission. The rewarming GCS, CR, PR, BE and rSO2 measurements were made after the patient's temperature reached 36 °C. Results: In survivors, the baseline rSO2 value was 67.5 (46-70) and the percent difference between baseline and rewarming rSO2 value was 0.03 (0.014-0.435). In non-survivors, the baseline rSO2 value was 30 (25-65) and the percent difference between baseline and rewarming rSO2 value was 0.031 (-0.08 to -20). No statistical difference was detected on percent changes between baseline and rewarming values of rSO2. Statistically significant difference was detected between baseline and rewarming GCS groups (p = 0.004). No statistical difference was detected between GCS, CR, PR, BE and rSO2 to determine the prognosis. Conclusion: Despite higher values of rSO2 on survivors than non-survivors, we found no statistically considerable difference between groups on baseline and the rewarming rSO2 values. Since the measurement is simple, and not affected by hypotension and hypothermia, the rSO2 may be a useful predictor for determining the prognosis after CPR.

Resumo Justificativa: Apesar dos novos avanços em reanimação cardiopulmonar (RCP), o dano cerebral muitas vezes ocorre após a reanimação. Objetivo: Avaliar o valor prognóstico de medir a saturação de oxigênio cerebral (rSO2) para estimar o prognóstico em pacientes após a reanimação cardiopulmonar. Projeto: Análise retrospectiva. Medidas e resultados: Foram avaliados após RCP 25 pacientes (12 do sexo feminino e 13 do masculino). Todos os pacientes foram submetidos à hipotermia (temperatura alvo de 33-34 °C). As mensurações da Escala de Coma de Glascow (GCS), dos reflexos corneanos (RC), dos reflexos pupilares (RP) e do excesso de base (EB) e rSO2 foram feitas na admissão. Na hipertermia, as mensurações de GCS, RC, RP, EB e rSO2 foram feitas depois que a temperatura atingiu 36 °C. Resultados: Em sobreviventes, o valor basal de rSO2 foi de 67,5 (46-70) e a diferença percentual entre o valor basal e a hipertermia de rSO2 foi de 0,03 (0,014-0,435). Em não sobreviventes, o valor basal de rSO2 foi de 30 (25-65) e a diferença percentual entre o valor basal de hipotermia de rSO2 foi de 0,031 (-0,08-20). Não houve diferença estatística nas variações percentuais entre os valores da rSO2 na fase basal e de reaquecimento. Uma diferença estatisticamente significativa foi observada entre os valores da GCS na fase basal e de reaquecimento dos grupos (p = 0,004). Não houve diferença estatisticamente significativa entre GCS, RC, RP, EB e rSO2 para determinar o prognóstico. Conclusão: Embora os valores da rSO2 tenham sido mais elevados em sobreviventes do que em não sobreviventes, não observamos uma diferença estatisticamente significativa dos valores da rSO2 entre os grupos na fase basal e de reaquecimento. Como a mensuração é simples, e não afetada por hipotensão e hipotermia, a rSO2 pode ser um indicador útil para determinar o prognóstico após a RCP.