Total Creatine Research Articles

Changes in aspartate metabolism in the medial-prefrontal cortex of nicotine addicts based on J-edited magnetic resonance spectroscopy.

This study aims to explore the changes of the aspartate (Asp) level in the medial-prefrontal cortex (mPFC) of subjects with nicotine addiction (nicotine addicts [NAs]) using the J-edited 1 H MR spectroscopy (MRS), which may provide a positive imaging evidence for intervention of NA. From March to August 2022, 45 males aged 40-60 years old were recruited from Henan Province, including 21 in NA and 24 in nonsmoker groups. All subjects underwent routine magnetic resonance imaging (MRI) and J-edited MRS scans on a 3.0 T MRI scanner. The Asp level in mPFC was quantified with reference to the total creatine (Asp/Cr) and water (Aspwater-corr , with correction of the brain tissue composition) signals, respectively. Two-tailed independent samples t-test was used to analyze the differences in levels of Asp and other coquantified metabolites (including total N-acetylaspartate [tNAA], total cholinine [tCho], total creatine [tCr], and myo-Inositol [mI]) between the two groups. Finally, the correlations of the Asp level with clinical characteristic assessment scales were performed using the Spearman criteria. Compared with the control group (n = 22), NAs (n = 18) had higher levels of Asp (Asp/Cr: p = .005; Aspwater-corr : p = .004) in the mPFC, and the level of Asp was positively correlated with the daily smoking amount (Asp/Cr: p < .001; Aspwater-corr : p = .004). No significant correlation was found between the level of Asp and the years of nicotine use, Fagerstrom Nicotine Dependence (FTND), Russell Reason for Smoking Questionnaire (RRSQ), or Barratt Impulsivity Scale (BIS-11) score. The elevated Asp level was observed in mPFC of NAs in contrast to nonsmokers, and the Asp level was positively correlated with the amount of daily smoking, which suggests that nicotine addiction may result in elevated Asp metabolism in the human brain.

The effect of contact/collision sport participation without concussion on neurometabolites: A systematic review and meta-analysis of magnetic resonance spectroscopy studies.

The aim of this study was to systematically review prior research investigating the effects of contact/collision sport participation on neurometabolite levels in the absence of concussion. Four online databases were searched to identify studies that measured neurometabolite levels in contact/collision sport athletes (without concussion) using proton (1 H) or phosphorus (31 P) magnetic resonance spectroscopy (MRS). All study designs were acceptable for inclusion. Meta-analytic procedures were used to quantify the effect of contact/collision sport participation on neurometabolite levels and explore the impact of specific moderating factors (where sufficient data were available). Narrative synthesis was used to describe outcomes that could not be meta-analysed. Nine observational studies involving 300 contact/collision sport athletes were identified. Six studies (providing 112 effect estimates) employed longitudinal (cohort) designs and three (that could not be meta-analysed) employed case-control designs. N-acetylaspartate (NAA; g = -0.331, p = 0.013) and total creatine (tCr; creatine + phosphocreatine; g = -0.524, p = 0.029), but not glutamate-glutamine (Glx), myo-inositol (mI) or total choline (tCho; choline-containing compounds; p's > 0.05), decreased between the pre-season and mid-/post-season period. Several moderators were statistically significant, including: sex (Glx: 6 female/23 male, g = -0.549, p = 0.013), sport played (Glx: 22 American football/4 association football [soccer], g = 0.724, p = 0.031), brain region (mI: 2 corpus callosum/9 motor cortex, g = -0.804, p = 0.015), and the MRS quantification approach (mI: 18 absolute/3 tCr-referenced, g = 0.619, p = 0.003; andtCho: 18 absolute/3 tCr-referenced, g = 0.554, p = 0.005). In case-control studies, contact/collision sport athletes had higher levels of mI, but not NAA or tCr compared to non-contact sport athletes and non-athlete controls. Overall, this review suggests that contact/collision sport participation has the potential to alter neurometabolites measured via 1 H MRS in the absence of concussion. However, further research employing more rigorous and consistent methodologies (e.g. interventional studies with consistent 1 H MRS pulse sequences and quantifications) is required to confirm and better understand the clinical relevance of observed effects.

Regional sex differences in neurochemical profiles of healthy mice measured by magnetic resonance spectroscopy at 9.4 tesla

ObjectiveTo determine sex differences in the neurochemical concentrations measured by in vivo proton magnetic resonance spectroscopy (1H MRS) of healthy mice on a genetic background commonly used for neurodegenerative disease models.Methods1H MRS data collected from wild type mice with C57BL/6 or related genetic backgrounds in seven prior studies were used in this retrospective analysis. To be included, data had to be collected at 9.4 tesla magnetic field using advanced 1H MRS protocols, with isoflurane anesthesia and similar animal handling protocols, and a similar number of datasets from male and female mice had to be available for the brain regions analyzed. Overall, 155 spectra from female mice and 166 spectra from male mice (321 in total), collected from six brain regions (brainstem, cerebellum, cortex, hippocampus, hypothalamus, and striatum) at various ages were included.ResultsConcentrations of taurine, total creatine (creatine + phosphocreatine), ascorbate, glucose and glutamate were consistently higher in male vs. female mice in most brain regions. Striatum was an exception with similar total creatine in male and female mice. The sex difference pattern in the hypothalamus was notably different from other regions. Interaction between sex and age was significant for total creatine and taurine in the cerebellum and hippocampus.ConclusionSex differences in regional neurochemical levels are small but significant and age-dependent, with consistent male–female differences across most brain regions. The neuroendocrine region hypothalamus displays a different pattern of sex differences in neurochemical levels. Differences in energy metabolism and cellular density may underlie the differences, with higher metabolic rates in females and higher osmoregulatory and antioxidant capacity in males.

Serum cardiac troponin I levels in adults with sickle cell disease visiting the University College Hospital, Ibadan, Nigeria

Abstract significant association between troponin I level in&#x0D; &#x0D; Recurrent vaso-occlusive crisis and haemolysis normally affect the lifestyle of patients with sickle cell disease. This may occur for a few hours or some weeks, making many of them to require hospital admission and blood transfusion, with inevitable financial implications on care givers. Due to its tissue specificity, cardiac troponin I and T have been claimed to be important in detecting cardiac damage even in the presence of elevated total creatine kinase (CK) and CK-MB that can likely occur in exercise-induced skeletal muscle damage. The significance of cardiac assessment in sickle cell patients was emphasized in a previous report which showed that evidence of mortality related to cardiovascular causes was often encountered during autopsy. This study aimed at accessing serum cardiac Troponin I (cTnI) in adult patients with sickle cell disease at University College Hospital, Ibadan. After written consents were obtained, 131 individuals above 18 years were recruited, 95 of which were sickle cell disease subjects and 36 were non-sickle cell disease controls. Mean age was 35.4years±SD=7.54years with age range of 19 to 56years for the sickle celled subjects and 36.8years±SD=9.11years with age range of 19 to 58 years for controls. Male to female ratio was approximately 2:1 for control and 2.4 :1 for sickle cell subjects. A total of 4(4.2%) sickle cell patients had abnormal troponin I level. There was a significant difference in mean troponin I level between sickle cell subjects and control, but there was no significant association between troponin I and haematological parameters of the sickle cell patients. The likelihood of the sickle cell subjects developing crisis is low, but there was no significant association significant association between troponin I level in sickle cell subjects and their haematological parameters, while there was a significant difference in mean troponin I between Sickle cell subjects and non-Sickle cell controls.

SLASER and PRESS perform similarly at revealing metabolite-age correlations at 3 T.

To compare the respective ability of PRESS and sLASER to reveal biological relationships, using age as a validation covariate at 3 T. MRS data were acquired from 102 healthy volunteers using PRESS and sLASER in centrum semiovale and posterior cingulate cortex (PCC). Acquisition parameters included TR/TE = 2000/30 ms, 96 transients, and 2048 datapoints sampled at 2 kHz. Spectra were analyzed using Osprey. SNR, FWHM linewidth of total creatine, and metabolite concentrations were extracted. A linear model was used to compare SNR and linewidth. Paired t-tests were used to assess differences in metabolite measurements between PRESS and sLASER. Correlations were used to evaluate the relationship between PRESS and sLASER metabolite estimates, as well as the strength of each metabolite-age relationship. Coefficients of variation were calculated to assess inter-subject variability in each metabolite measurement. SNR and linewidth were significantly higher (p < 0.01) for sLASER than PRESS in PCC. Paired t-tests showed significant differences between PRESS and sLASER in most metabolite measurements. PRESS-sLASER measurements were significantly correlated (p < 0.05) for most metabolites. Metabolite-age relationships were consistently identified using both methods. Similar coefficients of variation were observed for most metabolites. The study results suggest strong agreement between PRESS and sLASER in identifying relationships between brain metabolites and age in centrum semiovale and PCC data acquired at 3 T. sLASER is technically desirable due to the reduced chemical shift displacement artifact; however, PRESS performed similarly in homogeneous brain regions at clinical field strength.

Two years of newborn screening for Duchenne muscular dystrophy as a part of the statewide Early Check research program in North Carolina

PurposeCurrent and emerging treatments for Duchenne muscular dystrophy (DMD) position DMD as a candidate condition for newborn screening (NBS). In anticipation of the nomination of DMD for universal NBS, we conducted a prospective study under the Early Check voluntary NBS research program in North Carolina, United States. MethodsWe performed screening for creatine kinase-MM (CK-MM), a biomarker of muscle damage, on residual routine newborn dried blood spots (DBS) from participating newborns. Total creatine kinase testing and next generation sequencing of an 86-neuromuscular gene panel that included DMD were offered to parents of newborns who screened positive. Bivariate and multivariable analyses were performed to assess effects of biological and demographic predictors on CK-MM levels in DBS. ResultsWe screened 13,354 newborns and identified 2 males with DMD. The provisional 1626 ng/mL cutoff was raised to 2032 ng/mL to improve specificity, and additional cutoffs (900 and 360 ng/mL) were implemented to improve sensitivity for older and low-birthweight newborns. ConclusionPopulation-scale screening for elevated CK-MM in DBS is a feasible approach to identify newborns with DMD. Inclusion of birthweight- and age-specific cutoffs, repeat creatine kinase testing after 72 hours of age, and DMD sequencing improve sensitivity and specificity of screening.

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction.

Acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide and is characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR). However, the molecular mechanisms involved in these arrhythmias are still little understood. To investigate the cardioprotective role of the cardiac Ca2+/cAMP/adenosine signaling pathway in AMI, L-type Ca2+ channels (LTCC) were blocked with either nifedipine (NIF) or verapamil (VER), with or without A1-adenosine (ADO), receptors (A1R), antagonist (DPCPX), or cAMP efflux blocker probenecid (PROB), and the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by CIR in rats was evaluated. VA, AVB and LET incidences were evaluated by ECG analysis and compared between control (CIR group) and intravenously treated 5 min before CIR with NIF 1, 10, and 30 mg/kg and VER 1 mg/kg in the presence or absence of PROB 100 mg/kg or DPCPX 100 µg/kg. The serum levels of cardiac injury biomarkers total creatine kinase (CK) and CK-MB were quantified. Both NIF and VER treatment were able to attenuate cardiac arrhythmias caused by CIR; however, these antiarrhythmic effects were abolished by pretreatment with PROB and DPCPX. The total serum CK and CK-MB were similar in all groups. These results indicate that the pharmacological modulation of Ca2+/cAMP/ADO in cardiac cells by means of attenuation of Ca2+ influx via LTCC and the activation of A1R by endogenous ADO could be a promising therapeutic strategy to reduce the incidence of severe and fatal arrhythmias caused by AMI in humans.

Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study

The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (1H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain 1H-MRS, while in dataset B 21 participants underwent paired brain 1H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain 18F-FDG-PET and 1H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.

Spectroscopic abnormalities in the pregenual anterior cingulate cortex in obsessive-compulsive disorder using proton magnetic resonance spectroscopy: a controlled study

BackgroundThe main aim of the present study is to determine the role of metabolites observed using proton magnetic resonance spectroscopy (1H-MRS) in obsessive-compulsive disorder (OCD). As the literature describing biochemical changes in OCD yields conflicting results, we focused on accurate metabolite quantification of total N-acetyl aspartate (tNAA), total creatine (tCr), total choline-containing compounds (tCh), and myo-inositol (mI) in the anterior cingulate cortex (ACC) to capture the small metabolic changes between OCD patients and controls and between OCD patients with and without medication.MethodsIn total 46 patients with OCD and 46 healthy controls (HC) matched for age and sex were included in the study. The severity of symptoms in the OCD was evaluated on the day of magnetic resonance imaging (MRI) using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Subjects underwent 1H-MRS from the pregenual ACC (pgACC) region to calculate concentrations of tNAA, tCr, tCho, and mI. Twenty-eight OCD and 28 HC subjects were included in the statistical analysis. We compared differences between groups for all selected metabolites and in OCD patients we analyzed the relationship between metabolite levels and symptom severity, medication status, age, and the duration of illness.ResultsSignificant decreases in tCr (U = 253.00, p = 0.022) and mI (U = 197.00, p = 0.001) in the pgACC were observed in the OCD group. No statistically significant differences were found in tNAA and tCho levels; however, tCho revealed a trend towards lower concentrations in OCD patients (U = 278.00, p = 0.062). Metabolic concentrations showed no significant correlations with the age and duration of illness. The correlation statistics found a significant negative correlation between tCr levels and YBOCS compulsions subscale (cor = -0.380, p = 0.046). tCho and YBOCS compulsions subscale showed a trend towards a negative correlation (cor = -0.351, p = 0.067). Analysis of subgroups with or without medication showed no differences.ConclusionsPatients with OCD present metabolic disruption in the pgACC. The decrease in tCr shows an important relationship with OCD symptomatology. tCr as a marker of cerebral bioenergetics may also be considered as a biomarker of the severity of compulsions. The study failed to prove that metabolic changes correlate with the medication status or the duration of illness. It seems that a disruption in the balance between these metabolites and their transmission may play a role in the pathophysiology of OCD.

Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments.

1H-magnetic resonance spectroscopy (1H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1H-MRS and their association with clinical disability in SPMS. Longitudinal. 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = -0.21); in the riluzole arm, GM Glx (β = -0.25) and Glx/tCr (β = -0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. 1H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. 1 TECHNICAL EFFICACY: Stage 4.

Comparative study of bilateral putamen for patients with severe Parkinson's disease detected by 1H magnetic resonance spectroscopy.

The diagnosis of Parkinson's disease (PD) is challenging because the clinical symptoms overlap with other neurodegenerative diseases. The discovery of reliable biomarkers is highly expected to facilitate clinical diagnosis. Through the analysis of the 1H magnetic resonance spectroscopy (1H-MRS) in the putamen, the purpose of the study was to discuss the possibility of the difference in metabolite concentrations between the left and right putamen as biomarkers for patients with severe PD. We collected 1H-MRS of unilateral or bilateral putamen from 41 patients and used the independent sample t-test and paired t-test to analyze 4 metabolite concentrations, including choline (Cho), total N-acetyl aspartate (tNAA), total creatine (tCr), and combined glutamate and glutamine; Bonferroni correction was used to correct P values for multiple comparisons. We designed 4 controlled experiments as follows: (I) PD patients versus healthy controls (HCs) in the left putamen; (II) PD patients versus HCs in the right putamen; (III) the left putamen versus the right putamen for PD patients; and (IV) the left putamen versus the right putamen for HCs. No statistically significant differences (P>0.05) were detected among 4 metabolites in the ipsilateral and bilateral putamen for the PD and HCs groups, except for tCr in the left putamen (PD 6.426±0.557, HCs 6.026±0.460, P=0.046) for ipsilateral comparisons. In the bilateral putamen of severe PD patients, there was no statistically significant difference in the 4 metabolites. The difference (P<0.05) in tCr in the left putamen might be a potential biomarker to distinguish HCs from severe patients in clinic. This might provide a reference for the clinical diagnosis and acquisition strategy of 1H-MRS in severe PD.

Anti-Atherosclerosis and Anti-Hyperlipidemia Functions of Terminalia catappa Fruit.

Background: Atherosclerosis is a chronic pathological condition that has remained clinically silent for decades, and the epidemic has continued to be on the rise due to risk factors, including diet, lifestyle, hyperlipidemia, pathogenic microorganisms, and aging. Using various synthetic drugs in treating atherosclerosis is associated with a high risk of myositis, angioedema, myoglobinuria, and acute renal failure. Various side effects of the available drugs have been reported; attempts are underway to explore natural sources with antiatherosclerotic activity. Aim and objective: Using a diet-induced atherosclerosis rat model, the current study tested the hypothesis of antiatherosclerotic and antihyperlipidemic roles of Terminalia catappa fruit extracts. Materials and Methods: Atherosclerosis in Wistar rats was induced using an atherogenic diet. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), creatine kinase (CK), and lactate dehydrogenase (LDH) were determined using analytical kits. Results: Quantitative phytochemical analysis of the extracts demonstrated that the plant had flavonoids, saponins, tannins, terpenoids, alkaloids, cardiac glycosides, sterols, phenols, and anthraquinones. Diet-induced atherogenic Wistar rats showed a significant (p < 0.05) increase in total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol compared to the healthy control group; however, the atherogenic lipid profile was reversed by the treatment of T. catappa fruit extracts. The biochemical experiments demonstrate that T. catappa fruit extracts have an antihyperlipidaemic effect, shown by a decreased coronary risk index and the atherogenic index, and an increased cardioprotective index, compared to disease control. Conclusion: The current study indicates that T. catappa fruit extracts may contain bioactive molecules to treat atherosclerosis.

Searching for Effective Methods of Diagnosing Nervous System Lesions in Patients with Alström and Bardet-Biedl Syndromes.

Bardet-Biedl syndrome (BBS) and Alström syndrome (ALMS) are rare multisystem diseases with an autosomal recessive mode of inheritance and genetic heterogeneity, characterized by visual impairment, hearing impairment, cardiomyopathy, childhood obesity, and insulin resistance. The purpose of our study was to evaluate the indicators of nervous system changes occurring in patients with ALMS and BBS using optical coherence tomography (OCT) and magnetic resonance spectroscopy (MRS) methods compared to a group of healthy subjects. The OCT results showed significantly lower macular thickness in the patient group compared to the control group (p = 0.002). The MRS study observed differences in metabolite levels between the study and control groups in brain areas such as the cerebellum, thalamus, and white matter. After summing the concentrations from all areas, statistically significant results were obtained for N-acetylaspartate, total N-acetylaspartate, and total creatine. Concentrations of these metabolites were reduced in ALMS/BBS patients by 38% (p = 0.0004), 35% (p = 0.0008), and 28% (p = 0.0005), respectively. Our results may help to understand the pathophysiology of these rare diseases and identify strategies for new therapies.

Gut microbiota changes in horses with Chlamydia

BackgroundZoonotic diseases pose a significant threat to public health. Chlamydia, as an intracellular pathogen, can colonize the intestinal tract of humans and animals, changing the gut microbiota. However, only a few studies have evaluated alterations in the gut microbiota of horses infected with Chlamydia. Therefore, this study aimed to investigate gut microbiota and serum biochemical indicators in horses with Chlamydial infection (IG) and healthy horses (HG). Fecal and blood samples were collected from 16 horses (IG: 10; HG: 6) before morning feeding for the determination of gut microbiota and serum biochemical parameters.ResultsThe results showed that total globulin (GLB), alanine aminotransferase (ALT), and creatine kinase (CK) levels were significantly increased in IG compared with HG. Notably, the gut microbial diversity increased in IG compared with HG. Furthermore, Moraxellaceae and Akkermanisa abundance decreased in IG, while Streptococcus, Treponema, Prevotella, and Paraprevotella abundances (13 genera of bacterial species) increased. Compared with HG, carbohydrate metabolism increased in IG while amino acid metabolism decreased. In addition, the abundance of 18 genera of bacteria was associated with the level of five serum biochemical indicators.ConclusionsIn summary, this study elucidated the influence of Chlamydia infection in horses on the gut microbiota, unraveling consequential alterations in its composition and metabolic profile. Therefore, this study improves the understanding of Chlamydia-induced intestinal infections.

Assessment of neurotransmitter imbalances within the anterior cingulate cortex in women with primary dysmenorrhea: An initial proton magnetic resonance spectroscopy study

PurposeThe neural pathophysiology underlying primary dysmenorrhea (PDM), which leads to poor mode and changes in central pain modulatory systems, remains largely unknown. The objective of this study was to investigate the changes in glutamate/glutamine (Glx) and gamma-aminobutyric acid (GABA+) levels within anterior cingulate cortex (ACC), and their associations with clinical indicators in PDM women. MethodsUsing 3 T proton magnetic resonance spectroscopy (1H-MRS), we acquired and compared ACC-Glx and ACC-GABA+ levels in PDMs (N = 41) and age- and education-matched healthy controls (HCs) (N = 39) during both the menstrual and periovulatory phases, and between menstrual and periovulatory phases within each group. Total creatine (Cr referencing) level was used as an endogenous reference. The correlations of ACC-neurotransmitter levels with clinical characteristics and the correlations of ACC-Glx with ACC-GABA+ levels in the two groups were analyzed. ResultsCompared to HCs or the periovulatory phase, PDMs exhibited significantly increased ACC-Glx levels (p < 0.05) during the menstrual phase. Positive correlations between GABA+ and Glx levels (r = 0.385, p = 0.025) were found in PDMs during the menstrual phase. ACC-GABA+ levels were associated with self-rating distress scale (SDS) scores (GABA+/Cr: r = 0.369, p = 0.045) and pain catastrophizing scale (PCS) scores (GABA+/Cr: r = 0.373, p = 0.042) in PDM group in only the menstrual phase. ConclusionOur study represents the first report of ACC-GABA+/Glx imbalances in PDMs during the menstrual phase, which may underlie the mechanisms mediating depression and painful catastrophic symptoms.

Neurochemical Differences between 1p/19q Codeleted and Noncodeleted IDH-mutant Gliomas by in Vivo MR Spectroscopy.

Background Noninvasive identification of glioma subtypes is important for optimizing treatment strategies. Purpose To compare the in vivo neurochemical profiles between isocitrate dehydrogenase (IDH) 1-mutant 1p/19q codeleted gliomas and their noncodeleted counterparts measured by MR spectroscopy at 3.0 T with a point-resolved spectroscopy (PRESS) sequence optimized for D-2-hydroxyglutarate (2HG) detection. Materials and Methods Adults with IDH1-mutant gliomas were retrospectively included for this study from two university hospitals (inclusion period: January 2015 to July 2016 and September 2019 to June 2021, respectively) based on availability of 1p/19q codeletion status and a PRESS acquisition optimized for 2HG detection (echo time, 97 msec) at 3.0 T before any treatment. Spectral analysis was performed using LCModel and a simulated basis set. Metabolite quantification was performed using the water signal as a reference and correcting for water and metabolite longitudinal and transverse relaxation time constants. Concentration ratios were computed using total creatine (tCr) and total choline. A two-tailed unpaired t test was used to compare metabolite concentrations obtained in codeleted versus noncodeleted gliomas, accounting for multiple comparisons. Results Thirty-one adults (mean age, 39 years ± 8 [SD]; 19 male) were included, and 19 metabolites were quantified. Cystathionine concentration was higher in codeleted (n = 13) than noncodeleted (n = 18) gliomas when quantification was performed using the water signal or tCr as references (2.33 mM ± 0.98 vs 0.93 mM ± 0.94, and 0.34 mM ± 0.14 vs 0.14 mM ± 0.14, respectively; both P < .001). The sensitivity and specificity of PRESS to detect codeletion by means of cystathionine quantification were 92% and 61%, respectively. Other metabolites did not show evidence of a difference between groups (P > .05). Conclusion Higher cystathionine levels were detected in IDH1-mutant 1p/19q codeleted gliomas than in their noncodeleted counterparts with use of a PRESS sequence optimized for 2HG detection. Of 19 metabolites quantified, only cystathionine showed evidence of a difference in concentration between groups. Clinical trial registry no. NCT01703962 © RSNA, 2023 See also the editorial by Lin in this issue.

A comparative study of posterior cingulate metabolism in patients with mild cognitive impairment due to Parkinson's disease or Alzheimer's disease

Few comparative studies have assessed metabolic brain changes in cognitive impairment among neurodegenerative disorders, and the posterior cingulate cortex (PCC) is a metabolically active brain region with high involvement in multiple cognitive processes. Therefore, in this study, metabolic abnormalities of the PCC were compared in patients with mild cognitive impairment (MCI) due to Parkinson’s disease (PD) or Alzheimer’s disease (AD), as examined by proton magnetic resonance spectroscopy (1H-MRS). Thirty-eight patients with idiopathic PD, including 20 with mild cognitive impairment (PDMCI) and 18 with normal cognitive function (PDN), 18 patients with probable mild cognitive impairment (ADMCI), and 25 healthy elderly controls (HCs) were recruited and underwent PCC 1H-MRS scans. Compared with HCs, patients with PDMCI exhibited significantly reduced concentrations of N-acetyl aspartate (NAA), total NAA (tNAA), choline (Cho), glutathione (GSH), glutamate + glutamine (Glx) and total creatine (tCr), while ADMCI cases exhibited significantly elevated levels of myo-inositol (Ins) and Ins/tCr ratio, as well as reduced NAA/Ins ratio. No significant metabolic changes were detected in PDN subjects. Compared with ADMCI, reduced NAA, Ins and tCr concentrations were detected in PDMCI. Besides, ROC curve analysis revealed that tCr concentration could differentiate PDMCI from PDN with an AUC of 0.71, and NAA/Ins ratio could differentiate patients with MCI from controls with normal cognitive function with an AUC of 0.74. Patients with PDMCI and ADMCI exhibited distinct PCC metabolic 1H-MRS profiles. The findings suggested cognitively normal PD patients with low NAA and tCr in the PCC might be at risk of preclinical PDMCI, and Ins and/or NAA/MI ratio in the PCC should be reconsidered a possible biomarker of preclinical MCI in clinical practice. So, comparing PCC’s 1H-MRS profiles of cognitive impairment among neurodegenerative illnesses may provide useful information for better defining the disease process and elucidate possible treatment mechanisms.

Mexican tea (Dysphania ambrosioides (L.) Mosyakin & Clemants) seeds attenuate tourniquet-induced hind limb ischemia–reperfusion injury by modulating ROS and NLRP3 inflammasome pathways

The main pathophysiological mechanisms of hind limb ischemia–reperfusion injury (HLIRI) are increased oxidative stress and inflammation. The present study was designed to characterize the phytocontents of Dysphania ambrosioides (DA) seeds extract via LC-MS/MS and investigate its effect on left hindlimb IR injury and the underlying mechanisms. Thirty adult rats (n = 6 per group) were divided into five groups: Control group; HLIRI group, HLIRI + DA (100 mg/kg) group, HLIRI + DA (200 mg/kg) group, and HLIRI + cilostazol (30 mg/kg) group. HE staining’s of the left gastrocnemius muscle and left kidney was done. Renal function, and both total and muscle creatine kinases were measured in serum. Oxidative stress markers (MDA, SOD, Nrf2 and HO-1), inflammatory markers (NLRP3, IL-1β and TNF-α) and caspase-3 as an apoptotic marker were measured in left gastrocnemius muscle. We found that DA extract contains 60 metabolites and its pretreatment prevented left kidney and left gastrocnemius muscle damage and decreased oxidative stress markers, inflammatory markers, and caspase-3 levels, compared to the control group. Moreover, the effect of the extract was dose-dependent and better than that of the reference drug, cilostazol. This study suggested that D. ambrosioides seeds have a protective effect on HLIRI, which may be related to the antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Neuronal and Glial Metabolite Abnormalities in Participants With Persistent Neuropsychiatric Symptoms After COVID-19: A Brain Proton Magnetic Resonance Spectroscopy Study.

The aim of this study was to determine whether neurometabolite abnormalities indicating neuroinflammation and neuronal injury are detectable in individuals post-coronavirus disease 2019 (COVID-19) with persistent neuropsychiatric symptoms. All participants were studied with proton magnetic resonance spectroscopy at 3 T to assess neurometabolite concentrations (point-resolved spectroscopy, relaxation time/echo time = 3000/30 ms) in frontal white matter (FWM) and anterior cingulate cortex-gray matter (ACC-GM). Participants also completed the National Institutes of Health Toolbox cognition and motor batteries and selected modules from the Patient-Reported Outcomes Measurement Information System. Fifty-four participants were evaluated: 29 post-COVID-19 (mean ± SD age, 42.4 ± 12.3 years; approximately 8 months from COVID-19 diagnosis; 19 women) and 25 controls (age, 44.1 ± 12.3 years; 14 women). When compared with controls, the post-COVID-19 group had lower total N-acetyl compounds (tNAA; ACC-GM: -5.0%, P = .015; FWM: -4.4%, P = .13), FWM glutamate + glutamine (-9.5%, P = .001), and ACC-GM myo-inositol (-6.2%, P = .024). Additionally, only hospitalized patients post-COVID-19 showed age-related increases in myo-inositol, choline compounds, and total creatine (interaction P = .029 to <.001). Across all participants, lower FWM tNAA and higher ACC-GM myo-inositol predicted poorer performance on several cognitive measures (P = .001-.009), while lower ACC-GM tNAA predicted lower endurance on the 2-minute walk (P = .005). In participants post-COVID-19 with persistent neuropsychiatric symptoms, the lower-than-normal tNAA and glutamate + glutamine indicate neuronal injury, while the lower-than-normal myo-inositol reflects glial dysfunction, possibly related to mitochondrial dysfunction and oxidative stress in Post-COVID participants with persistent neuropsychiatric symptoms.

Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: A multi-modal magnetic resonance study.

Methadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. A number of clinical and animal model-based studies have reported cognitive deficits in infants prenatally exposed to methadone-based opioid treatments. However, the long-term impact of prenatal opioid exposure (POE) on pathophysiological mechanisms that govern neurodevelopmental impairment is not well understood. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of this study is to investigate the role of cerebral biochemistry and its possible association with regional microstructural organization in PME offspring. To understand these effects, 8-week-old male offspring with PME (n = 7) and prenatal saline exposure (PSE) (n = 7) were scanned in vivo on 9.4 Tesla small animal scanner. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the right dorsal striatum (RDS) region using a short echo time (TE) Stimulated Echo Acquisition Method (STEAM) sequence. Neurometabolite spectra from the RDS was first corrected for tissue T1 relaxation and then absolute quantification was performed using the unsuppressed water spectra. High-resolution in vivo diffusion MRI (dMRI) for region of interest (ROI) based microstructural quantification was also performed using a multi-shell dMRI sequence. Cerebral microstructure was characterized using diffusion tensor imaging (DTI) and Bingham-neurite orientation dispersion and density imaging (Bingham-NODDI). MRS results in the RDS showed significant decrease in N-acetyl aspartate (NAA), taurine (tau), glutathione (GSH), total creatine (tCr) and glutamate (Glu) concentration levels in PME, compared to PSE group. In the same RDS region, mean orientation dispersion index (ODI) and intracellular volume fraction (VFIC) demonstrated positive associations with tCr in PME group. ODI also exhibited significant positive association with Glu levels in PME offspring. Significant reduction in major neurotransmitter metabolites and energy metabolism along with strong association between the neurometabolites and perturbed regional microstructural complexity suggest a possible impaired neuroadaptation trajectory in PME offspring which could be persistent even into late adolescence and early adulthood.