Purpose
Acute ischemic stroke induces deoxyhemoglobin accumulation around the ischemic region while activating endothelial nitric oxide synthase (eNOS) coupling and the subsequent release of nitric ...oxide (NO). Because deoxyhemoglobin is a natural NO spin trap, its interplay with NO could be prominent during acute stroke. Its interaction with NO has been shown to induce overt paramagnetic signals in vitro; our goal was to investigate whether this interplay can be detected using MRI.
Methods
To verify the in vivo image effects using the deoxyhemoglobin‐NO interaction during acute stroke, eNOS states were manipulated in an animal model of acute ischemia, and the susceptibility signals, cerebral perfusion, and infarction were assessed noninvasively via MR susceptibility weighted imaging (SWI).
Results
Occlusion of the right middle cerebral artery increased eNOS coupling and susceptibility signals in the ischemic cortex while abolishing regional cerebral blood flow. Pharmacological eNOS blockage led to weakened susceptibility signals in the ischemic cortex as well as worsened tissue survival. Consistently, abolishment of eNOS coupling through genetic editing reduced the regional susceptibility signals in the ischemic cortex, causing large infarcts.
Conclusion
Upregulation of eNOS during acute ischemia sustains tissue viability through the interaction between NO and deoxyhemoglobin. This interplay can be traced in vivo using SWI and can be considered a sensitive marker revealing the delicate oxygenation status of the ischemic tissue, therefore, guiding the management of acute stroke in clinical settings.
Objective
Huntington disease (HD) is an inherited neurodegenerative disease caused by the mutant huntingtin gene (mHTT), which harbors expanded CAG repeats. We previously reported that the brain ...vessel density is higher in mice and patients with HD than in controls. The present study determines whether vascular function is altered in HD and characterizes the underlying mechanism.
Methods
The brain vessel density and vascular reactivity (VR) to carbogen challenge of HD mice were monitored by 3D ΔR2‐mMRA and blood oxygenation level–dependent (BOLD)/flow‐sensitive alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), respectively. The amount of vascular endothelial growth factor (VEGF)‐A and the pericyte coverage were determined by immunohistochemistry and enzyme‐linked immunosorbent assay in human and mouse brain sections, primary mouse astrocytes and pericytes, and human astrocytes derived from induced pluripotent stem cells.
Results
Expression of mHTT in astrocytes and neurons is sufficient to increase the brain vessel density in HD mice. BOLD and FAIR MRI revealed gradually impaired VR to carbogen in HD mice. Astrocytes from HD mice and patients contained more VEGF‐A, which triggers proliferation of endothelial cells and may be responsible for the augmented neurovascular changes. Moreover, an astrocytic inflammatory response, which reduces the survival of pericytes through an IκB kinase–dependent pathway, mediates the low pericyte coverage of blood vessels in HD brains.
Interpretation
Our findings suggest that the inflammation‐prone HD astrocytes provide less pericyte coverage by promoting angiogenesis and reducing the number of pericytes and that these changes can explain the inferior VR in HD mice. The resultant impaired VR might hinder cerebral hemodynamics and increase brain atrophy during HD progression. Ann Neurol 2015;78:178–192
Cellular magnetic resonance imaging (MRI) has been well-established for tracking neural progenitor cells (NPC). Superparamagnetic iron oxide nanoparticles (SPIONs) approved for clinical application ...are the most common agents used for labeling. Conventionally, transfection agents (TAs) were added with SPIONs to facilitate cell labeling because SPIONs in the native unmodified form were deemed inefficient for intracellular labeling. However, compelling evidence also shows that simple SPION incubation is not invariably ineffective. The labeling efficiency can be improved by prolonged incubation and elevated iron doses. The goal of the present study was to establish simple SPION incubation as an efficient intracellular labeling method. To this end, NPCs derived from the neonatal subventricular zone were incubated with SPIONs (Feridex®) and then evaluated in vitro with regard to the labeling efficiency and biological functions. The results showed that, following 48 hours of incubation at 75 µg/ml, nearly all NPCs exhibited visible SPION intake. Evidence from light microscopy, electron microscopy, chemical analysis, and magnetic resonance imaging confirmed the effectiveness of the labeling. Additionally, biological assays showed that the labeled NPCs exhibited unaffected viability, oxidative stress, apoptosis and differentiation. In the demonstrated in vivo cellular MRI experiment, the hypointensities representing the SPION labeled NPCs remained observable throughout the entire tracking period. The findings indicate that simple SPION incubation without the addition of TAs is an efficient intracellular magnetic labeling method. This simple approach may be considered as an alternative approach to the mainstream labeling method that involves the use of TAs.
Polylactic acid (PLA) possesses many advantages, especially biodegradability, and has subsequently been used in many regions. Unfortunately, its disadvantages, including its brittleness, become an ...obstacle to its application and constrain its development. In this study, Polystyrene‐b‐poly(ethylene‐co‐1‐butene)‐b‐polystyrene (SEBS) is used as the toughener and maleic anhydride grafted polypropylene (PP‐g‐MA) is used as the compatibilizer. The melt‐blending technique for polymers is employed to modify PLA in order to produce PLA/SEBS membranes. For PLA/SEBS membranes, the optimal matrices are made of a blending ratio of PLA/SEBS/PP‐g‐MA being 57/40/3. Next, polyhexamethylene guanidine hydrochloride (PHGH) is combined with the optimal membranes to form PLA/SEBS antibacterial membranes, the crystallinity, thermal properties, and antibacterial properties of which are examined to determine the effect of the PHGH content. The test results show that an appropriate content of SEBS or PHGH has a positive influence on PLA/SEBS antibacterial membranes. Moreover, the antibacterial membranes exhibit greater antibacterial efficacy against Escherichia coli (E. coli) than is gained with an increase in the PHGH content.
Background
Adipose tissue is closely related to bone mass, bone quality, and bone fractures, but the connection between fat and bone is complex and gender‐related. Fat–water magnetic resonance ...imaging (MRI) and MR spectroscopy (MRS) are very useful tools for identifying tissue fat.
Purpose
To assess gender interactions between bone mineral density (BMD), bone marrow fat, and body mass index (BMI) in the elderly using fat–water MRI and MRS.
Study Type
Prospective/cohort.
Population
Sixty‐six women and 38 men (mean age, 62.3 years; range, 50–75 years), Asian.
Field Strength
A 1.5T MR equipped with a body and spine array coil. STEAM MRS and T2* Dixon were performed.
Assessment
Vertebral bone marrow fat ratio (MFR), BMI, and BMD were measured. Correlations between these variables and differences in bone density in MFR were assessed between participants, divided into three groups based on bone density.
Statistical Tests
Multiple regression; Pearson tests; analysis of covariance; analysis of variance.
Results
Multiple regression analysis identified gender, vertebral bone MFR, and BMI as significant predictors of vertebral BMD (P < 0.001). Among the women, vertebral BMD was negatively correlated with vertebral MFR (P = 0.011), but among the men, it was positively correlated with BMI (P = 0.048), although this relationship was confounded by age and MFR. Moreover, vertebral bone marrow fat and BMI were indeed statistically uncorrelated in the elderly (P = 0.357 in women; P = 0.961 in men).
Data Conclusion
We found gender interactions between fat and bone in the elderly. Higher bone marrow fat was correlated with lower trabecular BMD in older women but not in men. On the other hand, the positive correlation between BMI and BMD was more pronounced in men than in women.
Level of Evidence: 2
Technical Efficacy Stage: 2
J. Magn. Reson. Imaging 2020;51:1382–1389.
Studies showed that the endotoxemia-related biomarker, lipopolysaccharide-binding protein (LBP), is associated with obesity and fatty liver. The level of LBP is reduced after surgical weight loss. ...This study aimed to verify the change of serum LBP levels after one-year medical weight management in subjects with obesity.
A total of 62 subjects with obesity, 39 subjects with overweight, and 21 subjects with normal body mass index were enrolled for a one-year weight management program. Basic information, body composition analysis, clinical data, serum LBP level, and abdominal ultrasonography findings were collected. At baseline, the serum LBP levels of the obese and overweight subjects were significantly higher than that of the normal group (30.9±7.4 and 29.6±6.3 versus 23.1±5.6 μg/mL, respectively, p<0.001). Serum LBP in subjects with obesity was significantly reduced to 26.5±7.1 μg/mL (p-value < 0.001) after one year. In the multivariate analyses, LBP was associated with high sensitive C-reactive protein (hs-CRP) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) before weight management in the obese group. Moreover, the change of LBP in response to weight management was significantly related to the changes of hs-CRP, leukocyte count and NFS by multivariate linear regression analysis also in the obese group.
The serum level of the endotoxemia-related biomarker, LBP, decreases after one-year weight management in the obese subjects. In addition to serving as a metainflammatroy biomarker like hs-CRP, LBP may also be a potential biomarker as a non-invasive biomarker for the evaluation of liver fibrosis in NAFLD.
Gout is one of the most painful disease conditions. The central mechanism of pain processing in this condition remains elusive. Cerebral blood volume (CBV) responses are faithful correlates of brain ...activity changes; the application of CBV-weighted functional magnetic resonance imaging (fMRI) may shed light on the issue of interest. Transient receptor potential vanilloid 1 (TRPV1) is a critical ion channel expressed both peripherally in nociceptors and centrally in the brain. Whether TRPV1 plays a critical role in gout pain was also explored. Results showed that, in rats with gouty arthritis, noxious stimulation induced CBV increases in the primary somatosensory cortex and thalamus. These increases were correlated with up-regulated TRPV1 protein expression and pain behavior. Selective blockage of central TRPV1 channel activity by intrathecal administration of AMG9810 reversed the induced pain, and abolished the induced CBV increase in thalamocortical regions. The findings support that TRPV1 activation in the central pain pathway is crucial to the augmentation of pain in gouty conditions. This new information supports the development of TRPV1-based drugs for treating gout pain, while fMRI can be useful for repeated evaluation of brain activity changes induced by gout.
Functional magnetic resonance imaging (fMRI) has revolutionized investigations of brain functions. Increases in fMRI signals are usually correlated with neuronal activation, but diverse explanations ...have been proposed for negative fMRI responses, including decreases in neuronal activity, the vascular-steal effect, and large increases in oxygen consumption. These possible scenarios, although encompassing a wide range of potential neurovascular responses, cannot yet be used to interpret certain types of negative fMRI signals. Recent studies have found that intravenous injection of dopamine D(2) receptor (D2DR) agonist reduced the hemodynamic responses in the caudate-putamen (CPu); however, whether endogenous dopaminergic neurotransmission contributes to fMRI signals remains obscure. Since it has been suggested that the D2DR is involved in pain modulation, and the CPu shows equivocal fMRI signals during noxious stimulation, the present study established an animal model based on graded electrical stimulation to elicit different levels of nociception, and aimed to determine whether nociception-induced endogenous dopaminergic neurotransmission is sufficient to generate negative fMRI responses. Our results from cerebral blood volume (CBV)-weighted fMRI, Fos immunohistochemistry, and electrophysiological recording demonstrated a salient bilateral CBV decreases associated with heightened neuronal activity in the CPu induced by unilateral noxious electrical stimulation. In addition, preinjection of D2DR antagonist reduced the observed CBV decreases. Our findings reveal the role of the D2DR in regulating striatal vascular responses and suggest that endogenous neurotransmission-induced CBV decreases underlie negative fMRI signals. Hence, the influence of endogenous neurotransmission should be considered when interpreting fMRI data, especially in an area involved in strong vasoactive neurotransmission.
Most researchers have examined forms of loneliness as discrete and emotional distress. The approach proposed in this study captures the reality that many persons experience more than one dimension of ...loneliness-varying degrees coupled with their psychological well-being in a family context. This study explores the latent structure of loneliness during young adulthood and its association with psychological well-being, as well as how these are related to their family characteristics in adolescence.
Data are from 2,748 young people, a cohort sample from the Taiwan Youth Project (TYP). Loneliness was assessed by a 6-item de Jong-Gierveld short scale with emotional and social loneliness domains. We describe the clustering between loneliness domains and psychological well-being, namely depressive symptoms, self-esteem, suicidal thoughts, and alcohol use using latent class cluster analysis. In addition to incorporating the Taiwanese family context, multivariate multinomial logistic regression models included data on family cohesion and parental guan (parental control) in adolescence. This might be associated with choices in partnership and childbearing, and influence loneliness in young adulthood.
Our results demonstrate a three-cluster model of loneliness involving emotional loners, serious emotional loners, and severe emotional/social loners. We also found that a feeling of serious emotional loneliness and severe emotional/social loneliness were significantly associated with psychological well-being, even adjusting for individual characteristics. Among young adults who had a partner, the married adults were significantly less likely to feel serious emotional loneliness than those who were living alone. Furthermore, young adults with stronger family cohesion during early adolescence were less likely to suffer from serious emotional loneliness (Relative risk ratios RRR 0.77, 95% CI 0.65-0.91) and severe emotional/social loneliness (RRR 0.54, 95% CI 0.34-0.85) in young adulthood.
This measurement strategy provides a foundation for future research into how experts can address loneliness clusters in order to better understand psychological well-being during young adulthood and family context in adolescence. This is important because our results suggest that the various loneliness domains do not occur independently, but rather are embedded in patterns and are associated with family characteristics.
Intracerebral hemorrhage (ICH) is associated with high mortality and neurological deficits, and concurrent hyperglycemia usually worsens clinical outcomes. Aquaporin-4 (AQP-4) is important in ...cerebral water movement. Our aim was to investigate the role of AQP-4 in hyperglycemic ICH.
Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) in adult Sprague-Dawley male rats. ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. One set of rats was repeatedly monitored by MRI at 1, 4, and 7 days after ICH induction so as to acquire information on the formation of hematoma and edema. Another set of rats was killed and brains were examined for differences in the degree of hemorrhage and edema, water content, blood-brain barrier destruction, and AQP-4 expression.
Hyperglycemia ICH rats exhibited increased brain water content, more severe blood-brain barrier destruction, and greater vasogenic edema as seen on diffusion-weighted MRI. Significant downregulation of AQP-4 was observed in STZ-treated rats after ICH as compared with non-STZ-treated rats. Apoptosis was greater on day 1 after ICH in STZ-treated rats.
The expression of AQP-4 in the brain is downregulated in hyperglycemic rats as compared with normoglycemic rats after ICH. This change is accompanied by increased vasogenic brain edema and more severe blood-brain barrier destruction.
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