The radiological incidents and terrorism have demanded the need for the development of rapid, precise, and non-invasive technique for detection and quantification of exposed dose of radiation. Though ...radiation induced metabolic markers have been thoroughly investigated, but reproducibility still needs to be elucidated. The present study aims at assessing the reliability and reproducibility of markers using nuclear magnetic resonance (NMR) spectroscopy and further deriving a logistic regression model based on these markers. C57BL/6 male mice (8-10 weeks) whole body γ-irradiated and sham irradiated controls were used. Urine samples collected at 24 h post dose were investigated using high resolution NMR spectroscopy and the datasets were analyzed using multivariate analysis. Fifteen distinguishable metabolites and 3 metabolic pathways (TCA cycle, taurine and hypotaurine metabolism, primary bile acid biosynthesis) were found to be amended. ROC curve and logistic regression was used to establish a diagnostic model as Logit (p) = log (p/1 - p) = -0.498 + 13.771 (tau) - 3.412 (citrate) - 34.461 (α-KG) + 515.183 (fumarate) with a sensitivity and specificity of 1.00 and 0.964 respectively. The findings demonstrate the proof of concept and the potential of NMR based metabolomics to establish a prediction model that can be implemented as a promising mass screening tool during triage.
The majority of human mild traumatic brain injuries (mTBI; 70%) lack radiological evidence of injury, yet may present long term cognitive, and behavioral dysfunctions. With the hypothesis of evident ...damaged neural tissue and immunological consequences during acute phase of mTBI, we used closed skull weight-drop TBI model to address human mTBI condition. Serum cytokines (TNF-α, IL-10) and glial fibrillary acidic protein (GFAP) expression were examined at day 0 (control, pre-injury), 4h, day 1, day 3 and day 5 post injury (PI). Diffusion tensor imaging (DTI) was performed at similar timepoints to identify neuroinflammation translation into imaging abnormalities and monitor injury progression. DTI indices including mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy and axial diffusivity values were quantified from cortex (CTX), hippocampus and corpus callosum regions. One way ANOVA showed significant increase in TNF-α at 4h and IL-10 at day 1 PI as compared to control. GFAP+ cells were significantly increased at day 3 and day 5 as compared to control in CTX. Repeated measures ANOVA revealed significant decreases in MD, RD values in CTX at day 3 and day 5 as compared to day 0. A significant, inverse correlation was observed between cortical MD (r=−0.74, p=0.01), AD (r=−0.60, p=0.03) and RD (r=−0.72, p=0.01) values with mean GFAP+ cells in the cortical region. These findings suggest that mTBI leads to elevated cytokine expression and subsequent hypertrophy of astrocytic processes. The increased numbers of reactive glial cells contribute diffusion restrictions in the CNS leading to reduced MD and RD values. These findings are in line with the deficits and pathologies associated with clinical mTBI, and support the use of mTBI model to address pathology and therapeutic options.
•Reduced mean diffusivity and radial diffusivity was observed in cortex region at day 3 and day 5 post injury in rodent model of mild TBI.•Significant correlation was observed between increased GFAP expression and DTI indices during acute phase of mTBI.•This study suggest that MD and RD are potential markers of injury and may help in assessing/monitoring of mTBI during acute phase of injury.•Present findings corroborate with deficits and pathologies in clinical mTBI, and support the model to address pathology and therapeutic options.
Purpose:
Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These ...neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (
1
H MRS).
Materials and Methods:
We collected neuropsychological and
1
H MRS data from posterior parietal cortex and DLPFC, in both control (
N
= 30) and hyperthyroid (
N
= 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired
t
-test was applied in patients at baseline and follow-up. Spearman’s rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment.
Results:
Our results revealed a significant decrease in choline/creatine glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr) in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (
N
-acetyl aspartate +
N
-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment.
Conclusion:
The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.
Abstract Chronic alcohol abuse is characterized by impaired cognitive abilities with a more severe deficit in visual than in verbal functions. Neuropathologically, it is associated with widespread ...brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The present study sought to increase current understanding of the impairment of visual processing abilities in alcohol-dependent subjects, and its correlation with white matter microstructural alterations, using diffusion tensor imaging (DTI). To that end, a DTI study was carried out on 35 alcohol-dependent subjects and 30 healthy male control subjects. Neuropsychological tests were assessed for visual processing skills and deficits were reported as raw dysfunction scores (rDyS). Reduced FA (fractional anisotropy) and increased MD (mean diffusivity) were observed bilaterally in inferior and superior fronto-occipital fasciculus (FOF) fiber bundles. A significant inverse correlation in rDyS and FA values was observed in these fiber tracts whereas a positive correlation of these scores was found with the MD values. Our results suggest that FOF fiber bundles linking the frontal lobe to occipital lobe might be related to visual processing skills. This is the first report of an alteration of the white matter microstructure of FOF fiber bundles that might have functional consequences for visual processing in alcohol-dependent subjects who exhibit no neurological complications.
Neuropsychological studies have reported that attention, memory, language, motor and emotion processing are impaired in schizophrenia. It is known that schizophrenia involves structural alterations ...in the white matter of brain that contribute to the pathophysiology of the disorder. Uncinate fasciculus (UNC), a bundle of white matter fibres, plays an important role in the pathology of this disorder and involved in cognitive functions such as memory, language and emotion processing. Therefore, the present study aimed to investigate microstructural changes in UNC fibre in schizophrenia patients relative to controls and its correlation with neuropsychological scores.
Diffusion tensor imaging (DTI) and Hindi version of Penn Computerised Neuropsychological Battery test was performed in 14 schizophrenia patients and 14 controls. DTI measures fractional anisotropy (FA) and mean diffusivity (MD) from UNC fibre were calculated and a comparison was made between patients and controls. Pearson’s correlation was performed between neuropsychological scores and DTI measures.
Schizophrenia patients showed significantly reduced FA values in UNC fibre compared to controls. In schizophrenia patients, a positive correlation of attention, spatial memory, sensorimotor dexterity and emotion with FA was observed. These findings suggest that microstructural changes in UNC fibre may contribute to underlying dysfunction in the cognitive functions associated with schizophrenia.
Somatosensory cortex of adult primates undergoes topographic reorganization following spinal cord or peripheral nerve injuries. Electrophysiological studies in monkeys show that after chronic lesions ...of dorsal columns of the spinal cord at cervical levels, there is an expansion of face representation into the deafferented hand region of area 3b of cortex. However, these techniques can sample only a limited portion of the brain. In order to help understand mechanisms of brain reorganization use of noninvasive tools in non-human primate experimental model is important. Use of blood oxygen level dependent-functional magnetic resonance imaging (BOLD-fMRI) to study brain reorganization in non-human primates has been extremely limited. Here, we show that in monkeys with long-term unilateral lesions of the dorsal columns at cervical levels, tactile stimulation of the chin showed BOLD activation in the deafferented hand region of contralesional area 3b in the post-central gyrus. In a monkey with a partial lesion of the dorsal columns, stimulations of both hand and chin activated the partially deafferented hand region. We also show that the somatotopic organization in the non-deafferented ipsilesional somatosensory cortex remained normal.
Abstract Objective To investigate structural reorganization in the brain with differential visual experience using Voxel-Based Morphometry with Diffeomorphic Anatomic Registration Through ...Exponentiated Lie algebra algorithm (DARTEL) approach. Materials and methods High resolution structural MR images were taken in fifteen normal sighted healthy controls, thirteen totally blind subjects and six partial blind subjects. The analysis was carried out using SPM8 software on MATLAB 7.6.0 platform. Results VBM study revealed gray matter volume atrophy in the cerebellum and left inferior parietal cortex in total blind subjects and in left inferior parietal cortex, right caudate nucleus, and left primary visual cortex in partial blind subjects as compared to controls. White matter volume loss was found in calcarine gyrus in total blind subjects and Thlamus-somatosensory region in partially blind subjects as compared to controls. Besides, an increase in Gray Matter volume was also found in left middle occipital and middle frontal gyrus and right entorhinal cortex, and an increase in White Matter volume was found in superior frontal gyrus, left middle temporal gyrus and right Heschl's gyrus in totally blind subjects as compared to controls. Comparison between total and partial blind subjects revealed a greater Gray Matter volume in left cerebellum of partial blinds and left Brodmann area 18 of total blind subjects. Conclusion Results suggest that, loss of vision at an early age can induce significant structural reorganization on account of the loss of visual input. These plastic changes are different in early onset of total blindness as compared to partial blindness.
The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress towards extreme ...environment related diseases. Rarely has the high-altitude biology been studied using system sciences and omics high-throughput technologies.
In the present study, 1H-NMR-based metabolomics, along with multivariate analysis, were employed in a preclinical rat model to characterise the serum metabolic changes under chronic hypobaric hypoxia (HH) stress.
Rats were exposed to simulated hypobaric hypoxia equivalent of 6700 m above the sea level. The serum samples were collected from control and HH-exposure (7, 14, and 21 days) of hypobaric hypoxia.
The 1H-NMR metabolomics of the serum showed alterations in the metabolism of membranes, amino-acids altered cellular bioenergetics and osmoregulation. Multivariate statistical analysis revealed alterations in acetoacetate, choline, glutamine, acetate, betaine, ketone bodies and branched amino acid metabolites.
Present findings establishes the fingerprint biomarkers for chronic environmental hypoxia which will help in understanding extreme environment related health problems, early detection and developing strategies to clinically address high altitude hypoxia.
Cellular transplantation of stem cells can be a beneficial treatment approach for neurodegenerative diseases such as traumatic brain injury (TBI). In this study, we investigated the proliferation and ...differentiation potential of infused mesenchymal stem cells (MSCs) after localisation at the injury site. We evaluated the appropriate homing of infused MSCs through immunohistochemistry, followed by Y‐chromosome–specific polymerase chain reaction and fluorescent in situ hybridisation analyses. The proliferation and differentiation of infused MSCs were analysed using exogenous cell tracer 5′‐bromo‐2′‐deoxyuridine (BrdU) labelling and neuronal specific markers, respectively. Structural and functional recovery in TBI mice were examined by performing magnetic resonance imaging and different behavioural assessments, respectively. Results demonstrated a significantly high number of BrdU‐positive cells in the lesion region in the MSC‐infused group compared with control and TBI groups. Infused MSCs were well differentiated into neural‐like cells and expressed significantly more neural markers (neuronal nuclear antigen NeuN, microtubule‐associated protein 2 MAP2 and glial fibrillary acid protein GFAP). Improved tissue abnormalities as well as functional behaviours were observed in MSC‐infused TBI mice, implying the substantial proliferation and differentiation of infused MSCs. Our findings support the neuroprotective response and efficacy of MSCs after transplantation in TBI mice, and MSCs may serve as potential therapeutic candidates in regenerative medicine.
Infused MSCs were proliferated and well differentiated into neural‐like cells at lesion site, which correspondingly improved tissue abnormalities in TBI mice. The neuroprotective response and efficacy of MSCs may serve as potential therapeutic candidates in regenerative medicine.
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