Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events.

Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.

Occipital GABA levels in older adults and their relationship to visual perceptual suppression.

Several studies have attributed certain visual perceptual alterations in older adults to a likely decrease in GABA (Gamma Aminobutyric Acid) concentration in visual cortex, an assumption based on findings in aged non-human primates. However, to our knowledge, there is no direct evidence for an age-related decrease in GABA concentration in human visual cortex. Here, we estimated visual cortical GABA levels and Glx (combined estimate of glutamate and glutamine) levels using magnetic resonance spectroscopy. We also measured performance for two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion and binocular rivalry. Our results show increased visual cortical GABA levels, and reduced Glx levels, in older adults. Perceptual performance differed between younger and older groups for both tasks. When subjects of all ages were combined, visual cortical GABA levels but not Glx levels correlated with perceptual performance. No relationship was found between perception and GABA levels in dorsolateral prefrontal cortex. Perceptual measures and GABA were not correlated when either age group was considered separately. Our results challenge current assumptions regarding neurobiological changes that occur within the aging human visual cortex and their association with certain age-related changes in visual perception.

Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging.

Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepentaacetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24-48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology.NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.

Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve.

BACKGROUND: Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated. OBJECTIVE: In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves. METHODS: The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models. RESULTS: In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration. CONCLUSION: These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.

MRI-based glomerular morphology and pathology in whole human kidneys.

Nephron number (N(glom)) and size (V(glom)) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess N(glom) and V(glom) in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure N(glom) and V(glom) in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ~6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

[Identification of mutation in PAX9 gene in a Mongolian family with non-syndromic oligodontia].

OBJECTIVE: To investigate the mutation in transcription factor paired box gene PAX9 in a mongolian family with non-syndromic oligodontia. METHODS: Peripheral blood was collected from 17 core family members (9 unaffected, 8 affected) in this Mongolian family with non-syndromic oligodontia. Mutation in exons of PAX9 gene was identified by PCR amplification and DNA sequencing. RESULTS: A point mutation c.87G > C at position 87 in exon 4 of PAX9 was identified from 8 affected members in the family, which were G/C heterozygous.While the 9 healthy members in the family were homozygous for C which was consistent with normal reference sequence in the GenBank(accession number: NC_000014). CONCLUSIONS: The mutation of c.87G > C (p. Ala240Pro) in exon 4 of PAX9 was likely to cause the non-syndromic oligodontia in this Mongolian family.

Brain structural plasticity in survivors of a major earthquake.

BACKGROUND: Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. METHODS: Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13-25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. RESULTS: We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). LIMITATIONS: Differences in the variance of survivor and control data could impact study findings. CONCLUSION: Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal-limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal.

Impact of acute stress on human brain microstructure: An MR diffusion study of earthquake survivors.

A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self-rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and "SAS(-)" (SAS < 55 after correction) group. Thrity-two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel-based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self-rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors.

Diffusion tensor imaging characterization of occult brain damage in relapsing neuromyelitis optica using 3.0T magnetic resonance imaging techniques.

Studies of relapsing neuromyelitis optica (RNMO) using advanced MRI techniques are limited compared with those done on multiple sclerosis (MS). The present study used diffusion tensor imaging (DTI) to investigate whether occult brain damage exists in RNMO patients. DTI scans using a 3.0T MRI scanner were performed in 24 clinically confirmed RNMO patients whose conventional brain MRI results were normal, and also in 24 age- and sex-matched healthy control subjects. DTI data were processed to generate fractional anisotropy (FA) and mean diffusivity (MD) maps, and region of interest (ROI) analyses were performed to obtain these parameters in white matter (including medulla oblongata, cerebral peduncle, optic radiation, genu of corpus callosum, splenium of corpus callosum, and internal capsule) and gray matter (including thalamus and putamen). Regional measures from patients at stable and acute phases were compared with healthy controls. Both acute and stable NMO patients had a higher average FA in ROIs of the thalamus and putamen. Acute NMO patients had significantly higher average MDs than controls in the genu of corpus callosum and optic radiation, and significantly lower average MDs in the medulla oblongata. Stable NMO patients had increased MDs in the genu of corpus callosum and optic radiation, but lower MDs in the medulla oblongata, internal capsule and thalamus. The DTI findings confirm the presence of occult tissue damage in normal-appearance white and gray matter, especially deep gray matter, in RNMO patients. This study adds further to the evidence that DTI is suitable as a tool for characterizing subtle brain tissue damage.

Voxelwise meta-analysis of gray matter reduction in major depressive disorder.

BACKGROUND: Voxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD. METHODS: A systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD. RESULTS: A total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus. CONCLUSIONS: Meta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.

Abnormal spontaneous brain activity in medication-naïve ADHD children: a resting state fMRI study.

Abnormal baseline brain functional connectivity in attention-deficit/hyperactivity disorder (ADHD) has been revealed in a number of studies by using resting-state functional MRI (rfMRI). The aim of this study was to investigate the spontaneous frontal activities in medication-naïve ADHD boys using the rfMRI derived index, amplitude of low-frequency fluctuation (ALFF). In total 17 ADHD boys and 17 matched controls were recruited to undergo rfMRI scan on a 3.0T MRI system. For each subject, six oblique slices covering the frontal areas were acquired with a rapid sampling rate (TR=400ms). Functional images were processed in AFNI for calculation of ALFF and then group comparison was performed using voxel-based t-test. With a corrected threshold of p<0.05 determined by AlphaSim, we found that in comparison with controls, ADHD patients demonstrated higher ALFF values in the left superior frontal gyrus and sensorimotor cortex (SMC), and lower ALFF values in the bilateral anterior, middle cingulate and the right middle frontal gyrus (MFG). Significant correlations were found between patients' WSCT measures and the peak ALFF located in the right MFG (r=0.69, p=0.02), and the left SMC (r=0.65, p=0.03). Our results revealed abnormal frontal activities at resting state associated with underlying physiopathology of ADHD, and suggested the ALFF analysis to be a potential approach in further exploration of this disorder.

Evaluation of cell tracking effects for transplanted mesenchymal stem cells with jetPEI/Gd-DTPA complexes in animal models of hemorrhagic spinal cord injury.

Cell tracking using iron oxide nanoparticles has been well established in MRI. However, in experimental rat models, the intrinsic iron signal derived from erythrocytes masks the labeled cells. The research evaluated a clinically applied Gd-DTPA for T1-weighted positive enhancement for cell tracking in spinal cord injury (SCI) rat models. MSCs were labeled with jetPEI/Gd-DTPA particles to evaluate the transfection efficiency by MRI in vitro. Differentiation assays were carried out to evaluate the differentiation ability of Gd-DTPA-labeled MSCs. The Gd-DTPA-labeled MSCs were transplanted to rat SCI model and monitored by MRI in vivo. Fluorescence images were taken to confirm the MRI results. Behavior test was assessed with Basso, Beattie, and Bresnahan (BBB) scoring in 6weeks after cell transplantation. The Gd-labeled MSCs showed a significant increase in signal intensity in T1-weighted images. After local transplantation, Gd-DTPA-labeled MSCs could be detected in SCI rat models by the persistent T1-weighted positive enhancement from 3 to 14days. Under electronic microscope, Gd-DTPA/jetPEI complexes were mostly observed in cytoplasm. Fluorescence microscopy examination showed that the Gd-labeled MSCs survived and distributed within the injured spinal cord until 2weeks. The Gd-labeled MSCs were identified and tracked with MRI by cross and sagittal sections. The BBB scores of the rats with labeled MSCs transplantation were significantly higher than those of control rats. Our results demonstrated that Gd-DTPA is appropriate for cell tracking in rat model of SCI, indicating that an efficient and nontoxic label method with Gd-DTPA could properly track MSCs in hemorrhage animal models.

MRI findings of choroid plexus tumors in the cerebellum.

Choroid plexus tumors (CPTs) are uncommon primary intracranial tumors. Here, we describe two patients with CPTs of the cerebellum: one had a choroid plexus papilloma located in the left cerebellar hemisphere that presented as an irregular, lobulated and solid-cystic mass, whereas the other had a choroid plexus carcinoma that exhibited a poorly defined, mixed-intensity mass associated with invasion of adjacent brain parenchyma. Contrast-enhanced MR imaging showed prominent heterogeneous enhancement. CPTs should be considered in the differential diagnosis for irregular, heterogeneous and intensely enhancing masses that occur in the cerebellum.

Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI.

Treatment-refractory depression (TRD) represents a large proportion of the depressive population, yet has seldom been investigated using advanced imaging techniques. To characterize brain dysfunction in TRD, we performed resting-state functional MRI (rs-fMRI) on 22 TRD patients, along with 26 matched healthy subjects and 22 patients who were depressed but not treatment-refractory (NDD) as comparison groups. Results were analyzed using a data-driven approach known as Regional Homogeneity (ReHo) analysis which measures the synchronization of spontaneous fMRI signal oscillations within spatially neighboring voxels. Relative to healthy controls, both depressed groups showed high ReHo primarily within temporo-limbic structures, and more widespread low ReHo in frontal, parietal, posterior fusiform cortices, and caudate. TRD patients showed more cerebral regions with altered ReHo than did NDD. Moderate but significant correlations between the altered regional ReHo and measures of clinical severity were observed in some identified clusters. These findings shed light on the pathophysiological mechanisms underlying TRD and demonstrate the feasibility of using ReHo as a research and clinical tool to monitor persistent cerebral dysfunction in depression, although further work is necessary to compare different measures of brain function to elucidate the neural substrates of these ReHo abnormalities.

Influence of methylprednisolone on magnetic resonance and histological measures during cuprizone-induced demyelination.

MRI is widely used for routine assessment of the progression of white matter injury while patients receive therapeutic agents, such as the glucocorticoid agonist methylprednisolone (MP). Given this, it is important to determine whether MRI parameters are altered by MP treatment in the absence of changes in cellular and myelin pathology. In this study, we compared magnetic resonance and histological measures during myelin injury in mice with and without short duration MP administration. Mice were scanned with a 4.7T MRI scanner before and after MP or vehicle injections using T2WI and DTI sequences and histology was performed on the brains following the second scan. Comparison of post-injection to pre-injection MRI showed a reduced T2WI intensity in the CC and an attenuated response in ADC|| and ADC perpendicular in the MP group in comparison with the vehicle group. However, quantitative analyses of myelin staining, neurofilament intensity and oligodendrocyte and microglial density were not different between the MP and the vehicle groups, indicating that the short duration MP treatment did not alter cellular and myelin pathology. These data suggest that MP could confound the validity of paraclinical measures such as ADC|| and ADC perpendicular that are otherwise being touted as markers of either axonal integrity or myelin repair.

[Microstructural abnormalities of basal ganglia and thalamus in children with first-episode Tourette's syndrome: a diffusion tensor imaging study].

OBJECTIVE: To investigate the microstructural integrity of basal ganglia and thalamus in children with first episode drug-naive Tourette's syndrome (TS) by diffusion tensor imaging (DTI). METHODS: Ten right handed patients with TS (mean age = 8.1 +/- 2.7 years old, 7 males and 3 females) and 10 age and gender-matched healthy control subjects (mean age = 9.5 +/- 1.6 years old, 9 males and 1 female) were recruited. All of the participants had normal findings on conventional MRI. DTI was performed using a 3.0T MR scanner by employing a spin echo single-shot EPI sequence with 15 diffusion encoding directions. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were generated from each participant's DTI images using DTIStudio software. Bilateral regions of interest (ROI) for the caudate nucleus, putamen,globus pallidus and thalamus were manually traced through ROIEditor software on averaged DWI maps. The differences on DT-MRI variables (ADC, FA) between the two groups were compared using the SPSS13.0 software. Significance level was set at 0.05. RESULTS: Significant decrease in FA values in left globus pallidus and bilateral thalamus, and increase in ADC values in the bilateral caudate nucleus, bilateral putamen and bilateral thalamus were found in the children with TS compared with the normal controls. CONCLUSION: The results support the hypothesis of abnormalities in basal ganglia and thalamus in the pathophysiology of TS.

Localization of cerebral functional deficits in treatment-naive, first-episode schizophrenia using resting-state fMRI.

BACKGROUND: Spontaneous low-frequency fluctuations (LFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal have been shown to reflect cerebral spontaneous neural activity, and the present study attempts to explore the functional changes in the regional brain in patients with schizophrenia using the amplitude of the BOLD signals. METHODS: A total of 66 treatment-naïve, first-episode schizophrenia (FES) patients and 66 normal age- and sex-matched controls were recruited. Resting-state fMRIs were obtained using a gradient-echo echo-planar imaging sequence. The amplitude of LFF (ALFF) was calculated using REST software. Voxel-based analysis of the ALFF maps between control and patient groups was performed with twos-sample t-tests using SPM2. RESULTS: Compared to the controls, the FES group showed significantly decreased ALFF in the medial prefrontal lobe (MPFC) and significant increases in the ALFF in the left and right putamen. Significant positive correlations were observed between ALFF values in the bilateral putamen in both the patient and control groups. CONCLUSIONS: Alterations of the ALFF in the MPFC and putamen in FES observed in the present study suggest that the functional abnormalities of those areas are at an early stage of the disease.

Magnetization transfer imaging reveals the brain deficit in patients with treatment-refractory depression.

BACKGROUND: Studies on treatment resistant depression (TRD) using advanced magnetic resonance imaging techniques are very limited. METHODS: A group of 15 patients with clinically defined TRD and 15 matched healthy controls underwent magnetization transfer imaging (MTI) and T1-weighted (T1W) imaging. MTI data were processed and analyzed voxel-wised in SPM2. A voxel based morphometric (VBM) analysis was performed using T1W images. RESULTS: Reduced magnetization transfer ratio was observed in the TRD group relative to normal controls in the anterior cingulate, insula, caudate tail and amygdala-parahippocampal areas. All these regions were identified within the right hemisphere. VBM revealed no morphological abnormalities in the TRD group compared to the control group. Negative correlations were found between MRI and clinical measures in the inferior temporal gyrus. LIMITATIONS: The cross-sectional design and small sample size. CONCLUSIONS: The findings suggest that MTI is capable of identifying subtle brain abnormalities which underlie TRD and in general more sensitive than morphological measures.

[Effects of electro-warmed needle of inner-Mongolian medicine on serum TNF-alpha, ACTH and corticosterone contents in fatigue rats].

OBJECTIVE: To observe the effect of electro-warmed needle (EWN, of Inner-Mongolian medicine) on fatigue rats' behavior, hypothalamic-pituitary-adrenocortex (HPA) axis activity and immune system so as to reveal its neuro-endocrino-immune mechanism. METHODS: Male SD rats were randomized into control (n=20), model (n=20) and EWN (n=19) groups. Fatigue model was established by forcing the rat to swim in a water pool till exhaustion, once daily, continuously for 21 days. "Dinghui" (central spot over the bregmatic bone) and "Xinxue" (the center of the depression beneath the 7th thoracic vertebra) were punctured with silver needles which were warmed electrically by using a MLY-I Electrical Needle-warming Apparatus, once every 3 days, 7 sessions altogether. On the 21st day of modeling, swim-exhaustion duration (SED), and immobility time and struggle times in tail suspension test were measured. Twenty-four hours after the last swim, the rats' serum TNF-alpha, ACTH an corticosterone contents were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with control group SED, immobility time and struggle times in tail suspension test in model group decreased, increased and lowered respectively and significantly (P < 0.01, 0.05); while in comparison with model group, the first 2 indexes of EWN group increased and lowered respectively and significantly (P < 0.05). No significant difference was found between EWN and model groups in struggle times (P > 0.05). Compared with control group, serum TNF-alpha, ACTH and corticosterone contents in model group increased significantly (P < 0.01), while in comparison with model group, the 3 indexes of EWN group were significantly lower (P < 0.01, 0.05). CONCLUSION: EWN treatment can reduce fatigue-induced increase of serum TNF-alpha, ACTH and corticosterone levels, and raise motor ability, suggesting a favorable regulation of HPA axis and immune function after EWN and improvement of fatigue in fatigue

MRI identification of the rostral-caudal pattern of pathology within the corpus callosum in the cuprizone mouse model.

PURPOSE: To characterize and compare histological and MRI-based changes within the corpus callosum (CC) in the cuprizone mouse model of multiple sclerosis (MS). MATERIALS AND METHODS: A total of 12 C57/BL6 mice were fed cuprizone from eight weeks of age for four weeks. One cohort of six cuprizone and two control mice were scanned with a T2-weighted (T2W) sequence. The other cohort of six cuprizone and four control mice were scanned using a dual-echo sequence for T2-mapping and a diffusion-weighted sequence with two orthogonal diffusion encoding directions to calculate water diffusivities parallel and perpendicular to the CC fiber (apparent diffusion coefficients [ADC](parallel) and ADC(perpendicular)). After the mice were killed, the rostral-caudal pattern of CC demyelination and other pathologies were examined using Luxol Fast Blue, neurofilament staining, and immunohistochemistry for microglia and were correlated with MRI. RESULTS: In contrast to control mice, T2W imaging (T2WI) hyperintensity, reduced ADC(parallel), and elevated ADC(perpendicular) were detected in the CC of cuprizone-fed mice, particularly in the caudal segment. The T2 value was increased in the entire CC. Marked demyelination, as well as axonal injury, microglia accumulation, and cellular infiltration were found in the caudal section of the cuprizone mouse CC. The rostral-caudal pattern of abnormalities within the CC in MRI measurements correlated well with histopathological findings. CONCLUSION: Noninvasive MRI using quantitative T2 and ADC mapping accurately characterized the rostral-caudal pattern of CC demyelination and other pathologies in cuprizone challenged mice, and thus could provide an effective way to assess the structural response to experimental therapeutics being designed for the treatment of MS.