BACKGROUNDIn head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been fully understood, while the alternations could be sensitively detected by proton (1H) nuclear magnetic resonance spectroscopy (MRS). In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term follow-up after radiation treatment using MRS in vivo.

METHODSA total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain (field size: 1.0 cm × 2.0 cm; anterior limit: binocular posterior inner canthus connection; posterior limit: external acoustic meatus connection; internal limit: sagittal suture). Conventional magnetic resonance imaging and single-voxel 1H-MRS were performed at different time points (in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation) to investigate the alternations in irradiation field. N-acetylaspartate/choline (NAA/Cho), NAA/creatinine (Cr), and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test.

RESULTSSignificant changes in the ratios of NAA/Cho (F = 57.37, P_{g < 0.001), NAA/Cr (F = 54.49, Pg < 0.001), and Cho/Cr (F = 9.78, Pg = 0.005) between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were significant differences in NAA/Cho (F = 9.17, Pt < 0.001) and NAA/Cr (F = 13.04, Pt < 0.001) ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides.}

CONCLUSIONSMRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries.

Animals ; Aspartic Acid ; analogs & derivatives ; metabolism ; Brain ; radiation effects ; Choline ; metabolism ; Male ; Proton Magnetic Resonance Spectroscopy ; methods ; Radiation Injuries ; diagnosis ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo determine whether there are in vivo differences of metabolites levels in bilateral cortical masticatory area(CMA) of patients with sleep bruxism, compared with healthy controls using proton magnetic resonance spectroscopy(1H-MRS). Accordingly to explore if cortical control of the central jaw motor system is abnormal in sleep bruxism patients.

METHODSFifteen sleep bruxism patients and fifteen age- and gender-matched healthy controls underwent 1H-MRS of bilateral CMA using J-difference edited point-resolved spectroscopy sequence(MEGA-PRESS) technique. Levels of metabolites were quantified from the ratio of the metabolite integral to the unsuppressed water signal. Differences of levels of γ-aminobutyric acid(GABA), glutmate(Glu) and N-acetyl aspartate(NAA) in bilateral CMA between sleep bruxism patients and healthy controls were tested using two-way ANOVA.

RESULTSEdited spectra were successfully obtained from the bilateral CMA in all of the participants. Levels of GABA+, glutmate and NAA in right and left CMA in sleep bruxism patients were (2.45±0.48)×10(-3), (2.35±0.62)×10(-3), (10.65±1.84)×10(-3), (10.49±2.37)×10(-3), (10.70±3.61)×10(-3), and (11.26±4.01)×10(-3) respectively. In contrast, levels of GABA+, glutmate and NAA in right and left CMA in healthy controls were (2.63±0.68)×10(-3), (2.65±0.97)×10(-3), (11.19± 1.34)×10(-3), (10.58±3.14)×10(-3), (11.82±1.80)×10(-3), and (11.95±3.23)×10(-3). There were no differences in levels of GABA+(P=0.196), Glu(P=0.590), and NAA(P=0.292) between sleep bruxism patients and healthy controls, nor in inbilateral CMA(GABA+: P=0.837; Glu: P=0.510; NAA: P=0.628).

CONCLUSIONSThe results indicate the absence of any alteration of the cortical control of the central jaw motor system in the levels of GABA, Glu and NAA in patients with sleep bruxism.

Analysis of Variance ; Aspartic Acid ; analogs & derivatives ; analysis ; metabolism ; Case-Control Studies ; Glutamic Acid ; analysis ; metabolism ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; methods ; Masticatory Muscles ; metabolism ; physiopathology ; Motor Neurons ; metabolism ; Sleep Bruxism ; metabolism ; physiopathology ; gamma-Aminobutyric Acid ; analysis ; metabolism

OBJECTIVE: To explore the correlation between diabetic nephropathy (DN) and cognitive impairment through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus patients at different stages of renal function.
 METHODS: Eighty six patients with Type 2 diabetes mellitus (T2DM) were enrolled for this study. According to the urinary albumin excretion rate (UAER), the patients were divided into a T2DM without DN group (DM group, n=33), an early DN group (DN-III group, n=26) and a clinical stage group (DN-IV group, n=27). Thirty healthy adults were selected as a control group (NC group). Biochemical indexes and UAER were measured, and glomerular filtration rate (GFR) was detected by single-photon emission computed tomography (SPECT). The cognitive function was measured by Montreal Cognitive Assessment (MoCA, Beijing version) and mini-mental state examination (MMSE). The peak areas of N-acetylasparte (NAA), creatine (Cr), choline-containing compounds (Cho) were detected by proton magnetic resonance spectroscopy (1H-MRS).
 RESULTS: 1) There was no statistical difference in MMSE scores between the DM group and the control group. The scores of MoCA in the DN-III group or in the DN-IV group were significant less than that in the NC group (F=3.66, P<0.05); 2) There was significant difference in left N-acetylaspartate (LNAA), left choline (LCho) among the diabetes groups. Compared with the DM group, the level of LNAA was decreased significantly (t=3.826, P<0.05) while the LCho was increased significantly (t=4.373, P<0.05) in the DN groups, with statistic difference between the 2 groups (t=3.693, P<0.05); 3) The MoCA scores of T2DM patients were negatively correlated with UAER (r=-0.285, P<0.05), while positively correlated with GFR (r=0.379, P<0.05); 4) Logistic regression analysis indicated that UAER and GFR were the major risky factors for diabetic cognitive impairment.
 CONCLUSION Diabetic cognitive impairment is closely correlated with the nephropathy in patients with Type 2 diabetes. With the decline in glomerular filtration function, the cognitive disorder tends to be aggravated. The hippocampal brain metabolism may have some changes in left side of Cho/Cr in patients with diabetic nephropathy.
Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Cerebrum ; metabolism ; Choline ; metabolism ; Cognition ; Cognition Disorders ; epidemiology ; Creatine ; metabolism ; Diabetes Mellitus, Type 2 ; physiopathology ; Diabetic Nephropathies ; epidemiology ; Glomerular Filtration Rate ; Humans ; Neuropsychological Tests

OBJECTIVE: To detect metabolic changes of bilateral frontal lobe in patients with multiple system atrophy (MSA) and cognitive dysfunction by 1H-proton magnetic resonance spectroscopy (1H-MRS).
 METHODS: N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr, myoinositol (mI)/Cr in three sides of frontal lobe were detected by 1H-MRS in 48 healthy controls, 23 patients with MSA and cognitive dysfunction and 19 patients with MSA but without cognitive dysfunction.
 RESULTS: NAA/Cr of bilateral frontal lobes in patients with MSA and cognitive dysfunction was significantly decreased compared with MSA patients without cognitive dysfunction and healthy controls (P<0.05). mI/Cr of right frontal lobes was significantly increased in patients with MSA and cognitive dysfunction compared with healthy controls (P<0.05). There was a negative correlation between NAA/Cr of bilateral frontal lobes and duration while a positive correlation between NAA/Cr of bilateral frontal lobes and MoCA score in patients with MSA and cognitive dysfunction.
 CONCLUSION There is a decrease in NAA/Cr and an increase in mI/Cr in frontal lobes in patients with MSA and cognitive dysfunction, which may be associated with cognitive dysfunction in MSA patients.
Aspartic Acid ; analogs & derivatives ; metabolism ; Choline ; metabolism ; Cognition Disorders ; physiopathology ; Creatine ; metabolism ; Frontal Lobe ; metabolism ; Humans ; Inositol ; metabolism ; Multiple System Atrophy ; physiopathology ; Proton Magnetic Resonance Spectroscopy

The purpose of this study is to explore depression metabolic markers in rat hippocampus and to investigate the anti-depressant effect of genipin and its mechanisms using nuclear magnetic resonance (NMR) metabonomics. Chronic unpredictable mild stress (CUMS) procedure was conducted to establish the depressive rat model. At the beginning of the third week, genipin low dose (25 mg x kg(-1)), middle dose (50 mg x kg(-1)), high dose (100 mg x kg(-1)), and venlafaxine (50 mg x kg(-1)) were given to the CUMS rats separately once daily for two weeks except control and model groups. Rat hippocampus was analyzed by 1H NMR based metabonomics after drug administration for 2 weeks. Significant differences in the metabolic profile of rat hippocampus of the CUMS treated group and the control group were observed with metabolic effects of CUMS including decreasing in glycine and N-acetylaspartate, increasing in inositol, glutamate, lactate, glutamine, taurine and alanine. Genipin showed ideal antidepressive effects at a dose of 50 mg x kg(-1) in rats, decrease of inositol, glutamate, lactate, alanine were observed, while glycine and N-acetylaspartate were increased. Important influence has been found on normal nervous system function of these significant changed metabolites, which suggests that the antidepressant effect of genipin may be played by enhancing the activity of neurons in hippocampus, repairing and improving the function of the neuron. The metabonomics approach is an effective tool for the investigation of the anti-depressant effect and pharmacologic mechanisms of genipin.
Alanine ; metabolism ; Animals ; Antidepressive Agents ; isolation & purification ; pharmacology ; Aspartic Acid ; analogs & derivatives ; metabolism ; Behavior, Animal ; drug effects ; Chronic Disease ; Depression ; drug therapy ; metabolism ; physiopathology ; Gardenia ; chemistry ; Glutamic Acid ; metabolism ; Glycine ; metabolism ; Hippocampus ; drug effects ; metabolism ; Inositol ; metabolism ; Iridoids ; isolation & purification ; pharmacology ; Lactic Acid ; metabolism ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the correlation of neurochemical metabolism in hippocampus with memory function in young adult patients with first-episode depression.

METHODSTwenty patients with first-episode depression (patient group) and fifteen health subjects (control group) were enrolled in the study. The neurochemical metabolism, including the levels of N-acetylaspartate (NAA), Choline (Cho), Creatine (Cr), Myoinositol (mI) were measured by proton magnetic resonance spectroscope (1H-MRS) in bilateral hippocampus. Wechsler Memory Scale (WMS) were used to examine the memory function in both groups.

RESULTSThe memory quotient (89.15 ±6.62) of patient group was significantly lower than that of controls (P <0.01),the scores of long-term memory,short-term memory and immediate memory in patients were also lower than those of controls (P<0.05 or 0.01). In patient group, the ratio of NAA/Cr (1.34 ±0.08) in the left hippocampus was significantly lower than that of control group (P<0.01); and the ratio of mI/Cr in the bilateral hippocampus [(0.63 ±0.13) in left and (0.6 ±0.1) in right] was significantly higher than those in control group (P<0.05). In patient group,the ratio of NAA/Cr in the left hippocampus was positively correlated with WMS scores (P<0.01), and the ratio of mI/Cr in the left hippocampus was negatively correlated with WMS scores (P<0.05).

CONCLUSIONThe memory deficit and abnormal metabolism function of neuron cell in hippocampus coexist in young adult patients with first-episode depression, and the lower NAA/Cr and higher mI/Cr ratio in the left hippocampus may result in the memory deficit.

Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Creatine ; metabolism ; Depressive Disorder ; metabolism ; physiopathology ; Female ; Hippocampus ; metabolism ; Humans ; Inositol ; metabolism ; Magnetic Resonance Spectroscopy ; Male ; Memory ; Neuropsychological Tests ; Young Adult

The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.
Adenocarcinoma ; metabolism ; pathology ; Administration, Intranasal ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; metabolism ; Aspartic Acid ; chemistry ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Curcumin ; administration & dosage ; metabolism ; Drug Carriers ; Ethylene Glycol ; chemistry ; toxicity ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Lysine ; chemistry ; toxicity ; Nanoparticles ; Particle Size ; Polyethylene Glycols ; chemistry ; toxicity ; Polyglutamic Acid ; analogs & derivatives ; chemistry ; toxicity

OBJECTIVETo study the changes in the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus metabolites in first-episode patients with positive symptoms of schizophrenia.

METHODSTwenty first-episode patients with positive symptoms of schizophrenia underwent diffusion tensor imaging (DTI) and proton multi-voxel spectroscopy (1H-MRS) examination. 1H-MRS images were obtained from two sides of the frontal white matter, the head of the hippocampus and the anterior cingulate fasciculus regions. The metabolites detected included N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and the ratios of NAA/Cr, Cho/Cr and NAA/Cho were determined. The fractional anisotropy (FA) values were measured in the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus.

RESULTSThe Cho/Cr ratio was significantly reduced in the left frontal white matter (1.18 ± 0.21) of the patients as compared to the right side (1.44 ± 0.34, P<0.05). In the left head of the hippocampus, NAA/Cr (1.34 ± 0.45) and Cho/Cr (1.41 ± 0.39) were significantly reduced compared to those of the right side (1.75 ± 0.15 and 1.76 ± 0.36, respectively, P<0.05). No significant differences in the metabolite levels were found between the left and right anterior cingulate fasciculus (P>0.05). DTI showed similar FA values between the left and right sides of the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus (P>0.05).

CONCLUSIONSPatients with positive symptoms of schizophrenia have diminished neuronal integrity and/or function in the left frontal white matter and head of the hippocampus, but not in the anterior cingulate fasciculus.

Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Brain ; metabolism ; physiopathology ; Choline ; metabolism ; Creatine ; metabolism ; Diffusion Tensor Imaging ; Female ; Gyrus Cinguli ; metabolism ; Hippocampus ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Schizophrenia ; metabolism ; physiopathology ; Young Adult

OBJECTIVETo study the metabolic changes of auditory cortex in patients with presbycusis by using proton magnetic resonance spectroscopy ((1)H-MRS).

METHODSTen normal hearing volunteers (youth group), 10 normal hearing of elderly (aged group) and 8 patients with presbycusis (presbycusis group) were checked with proton magnetic resonance spectroscopy. N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho), γ-aminobutyric acid (GABA), glutamic acid (Glu) compound were measured. The differences between the groups were semi-quantitatively analyzed.

RESULTSWhen compared with youth group, reduced NAA/Cr, increased Cho/Cr were found in the aged group and presbycusis group (P < 0.05). GABA/Cr ratio and Glu/Cr ratio were significant difference between presbycusis group and youth group (P < 0.05). There were no significant difference in the GABA/Cr and Glu/Cr ratios in the bilateral auditory cortex between the youth group and the aged group (P > 0.05). When compared with aged group, the metabolic changes of auditory cortex in patients with presbycusis were remarkable (P < 0.05).

CONCLUSIONS(1)H-MRS is a noninvasive technique that can provide useful information concerning the metabolic changes of auditory cortex in human. In comparison to the aged group and the youth group, the changes of NAA, GABA, Cho and Glu is found in auditory cortex in patients with presbycusis.

Adult ; Aged ; Aspartic Acid ; analogs & derivatives ; metabolism ; Auditory Cortex ; metabolism ; Case-Control Studies ; Choline ; metabolism ; Creatine ; metabolism ; Female ; Glutamic Acid ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Presbycusis ; metabolism ; pathology ; Young Adult ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVE: To examine the changes of metabolites in the bilateral thalamus of patients with secondarily generalized tonic-clonic seizure (SGTCS) and to explore the mechanism of SGTCS. METHODS: Thirty patients with SGTCS (epilepsy group) and 30 matched healthy controls (control group) were examined by 1H-magnetic resonance spectroscopy (1H-MRS). The levels of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine phosphocreatine (Cr-PCr), and myo-inositol (mI) of the bilateral thalamus were measured in both the epilepsy group and the control group. The ratios of NAA/Cr-PCr, NAA/(Cr-PCr+Cho), Cho/Cr-PCr and mI/Cr-PCr were compared and analyzed in the 2 groups. RESULTS: The ratios of NAA/Cr-PCr, and NAA/(Cr-PCr+Cho)(1.7074 ± 0.2214; 0.9333 ± 0.2173) in the left thalamus in the epilepsy group were significantly lower than those in the control group(1.8834 ±0.2093; 1.1243 ±0.2447)(P<0.05). The ratios of NAA/Cr-PCr, and NAA/(Cr- PCr+Cho) (1.7472 ±0.2439; 0.9165 ±0.2462) in the right thalamus in the epilepsy group were also significantly lower than those in the control group(1.8925 ± 0.2004; 1.0941 ± 0.2372)(P<0.05). There were no significant differences in the ratios of NAA/Cr-PCr, NAA/(Cr-PCr+Cho), Cho/Cr- PCr, and mI/Cr-PCr between the bilateral thalamis in the epilepsy group (P>0.05). CONCLUSION There is neuronal dysfunction in the bilateral thalamus in the epilepsy group. Abnormal changes of the bilateral thalamus are involved in the mechanism of SGTCS.
Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; analysis ; Brain Chemistry ; Case-Control Studies ; Choline ; analysis ; Energy Metabolism ; physiology ; Epilepsy, Generalized ; metabolism ; physiopathology ; Epilepsy, Tonic-Clonic ; metabolism ; physiopathology ; Female ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Thalamus ; metabolism ; physiopathology ; Young Adult