The Role of DNA Methylation in Stroke Recovery.

Epigenetic alterations affect the onset of ischemic stroke, brain injury after stroke, and mechanisms of poststroke recovery. In particular, DNA methylation can be dynamically altered by maintaining normal brain function or inducing abnormal brain damage. DNA methylation is regulated by DNA methyltransferase (DNMT), which promotes methylation, DNA demethylase, which removes methyl groups, and methyl-cytosine-phosphate-guanine-binding domain (MBD) protein, which binds methylated DNA and inhibits gene expression. Investigating the effects of modulating DNMT, TET, and MBD protein expression on neuronal cell death and neurorepair in ischemic stroke and elucidating the underlying mechanisms can facilitate the formulation of therapeutic strategies for neuroprotection and promotion of neuronal recovery after stroke. In this review, we summarize the role of DNA methylation in neuroprotection and neuronal recovery after stroke according to the current knowledge regarding the effects of DNA methylation on excitotoxicity, oxidative stress, apoptosis, neuroinflammation, and recovery after ischemic stroke. This review of the literature regarding the role of DNA methylation in neuroprotection and functional recovery after stroke may contribute to the development and application of novel therapeutic strategies for stroke.

Rodent Models of Post-Stroke Dementia.

Post-stroke cognitive impairment is one of the most common complications in stroke survivors. Concomitant vascular risk factors, including aging, diabetes mellitus, hypertension, dyslipidemia, or underlying pathologic conditions, such as chronic cerebral hypoperfusion, white matter hyperintensities, or Alzheimer's disease pathology, can predispose patients to develop post-stroke dementia (PSD). Given the various clinical conditions associated with PSD, a single animal model for PSD is not possible. Animal models of PSD that consider these diverse clinical situations have not been well-studied. In this literature review, diverse rodent models that simulate the various clinical conditions of PSD have been evaluated. Heterogeneous rodent models of PSD are classified into the following categories: surgical technique, special structure, and comorbid condition. The characteristics of individual models and their clinical significance are discussed in detail. Diverse rodent models mimicking the specific pathomechanisms of PSD could provide effective animal platforms for future studies investigating the characteristics and pathophysiology of PSD.

Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4+ and CD8+ T Cells through NF-κB p65 Signaling Pathway in Mice.

Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.

Hepatocyte-Specific Deficiency of DAX-1 Protects Mice from Acetaminophen-Induced Hepatotoxicity by Activating NRF2 Signaling.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.

Sicyos angulatus Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

Obesity is a medical condition in which excess body fat has accumulated to a serious extent. It is a chronic disease that can lead to dyslipidemia, insulin resistance, and type 2 diabetes. In the present study, we investigated the anti-obesity effects of Sicyos angulatus (SA) extract on a high-fat diet (HFD)-induced C57BL/6J obese mice. The mice were divided into vehicle and three SA groups (25, 50, and 100 mg/kg body weight). The mice were fed a HFD with or without SA for 12 weeks. The oral administration of SA reduced body and adipose tissue weight in HFD-fed mice compared to those in the vehicle group (p<0.05). Adipocyte size and inflammation significantly decreased in the SA-administered groups in a dose-dependent manner. In particular, adipocytes larger than 5000 µm2 were remarkably reduced by around 50% in the SA-treated groups (p<0.05). In addition, SA contributes towards reducing insulin resistance (measured as the HOMA-IR index) and glucose intolerance in HFD-induced obese mice (p<0.05; Vehicle 21.5±3.1 vs. SA100 4.7±0.4). These beneficial effects of SA on obesity may be linked to the suppression of lipogenesis and stimulating energy metabolism in white adipose tissue and muscle. In white adipose tissue and muscle, the administration of SA activated AMPK pathway, leading to the inhibition of the development of pathophysiological conditions associated with obesity, including lipogenesis and inflammation. These findings suggest that SA may prevent obesity through inhibiting fat accumulation in HFD-induced obese mice. Therefore, SA is able to exert metabolic benefits in the prevention of obesity and insulin resistance.

Shaping Rollable Display Devices: Effects of Gripping Condition, Device Thickness, and Hand Length on Bimanual Perceived Grip Comfort.

OBJECTIVE: To examine the effects of the gripping condition, device thickness, and hand length on bimanual perceived grip comfort associated with unrolling hand-held rollable screens. BACKGROUND: Rollable displays can be rolled and unrolled to change screen size. Although diverse rollable display device concepts have been suggested, little is known regarding ergonomic forms for comfortable screen unrolling. METHOD: Thirty young individuals (10 in each hand-length group) evaluated three rollable display device prototypes in three gripping conditions (no restriction on using side bezels, minimal use of side bezels, and restriction on the gripping type). Prototypes differed in their right-side thickness (2, 6, and 10 mm). Side bezel regions grasped during screen unrolling and corresponding bimanual grip comfort ratings were obtained. RESULTS: To improve perceived grip comfort and accommodate user-preferred gripping methods, rollable display devices should be 6 mm (preferably 10 mm) thick (vs. 2 mm) and have at least 20-mm-wide side bezels. Relative to device thickness, gripping conditions were more influential on grip comfort ratings. The "no restriction" condition improved grip comfort ratings and strengthened bimanual coupling in terms of grip comfort ratings. CONCLUSION: Contrary to current smartphone trends toward thinner and bezel-less designs, hand-held rollable display devices should be sufficiently thick and have sufficiently wide side bezels for screen unrolling. APPLICATION: Hand-held rollable display devices should be 6- or preferably 10-mm thick (vs. 2 mm) and have at least 20-mm-wide side bezels to ensure higher perceived grip comfort during bilateral screen unrolling.

Characterization of Tauopathy in a Rat Model of Post-Stroke Dementia Combining Acute Infarct and Chronic Cerebral Hypoperfusion.

Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated the cognitive impairment and pathomechanism associated with tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH). We performed middle cerebral artery occlusion (MCAO) surgery in rats to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic function. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was combined with MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the peri-infarct area when CCH was combined. Synergistic accentuation of tauopathy was evident in the white matter. Microtubules in the neuronal axon and myelin sheath showed partial colocalization with the hyperphosphorylated tau, whereas oligodendrocytes showed near-complete colocalization. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest a hypothesis that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through the glymphatic system. Therapeutic strategies to improve the clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.

Effects of Display Curvature, Presbyopia, and Task Duration on Visual Fatigue, Task Performance, and User Satisfaction.

OBJECTIVE: This study examined the effects of display curvature, presbyopia, and task duration on visual fatigue, task performance, and user satisfaction. BACKGROUND: Although curved displays have been applied to diverse display products, and some studies reported their benefits, it is still unknown whether the effects of display curvature are presbyopia-specific. METHOD: Each of 64 individuals (eight nonpresbyopes and eight presbyopes per display curvature) performed four 15-min proofreading tasks at one display curvature radius setting (600R, 1140R, 4000R, and flat; mm). Diverse measurements were obtained to assess visual fatigue, task performance, and user satisfaction. RESULTS: The mean pupil diameter was the largest with 1140R, indicating this curvature radius was associated with the least development of visual fatigue; 600R was comparable with 1140R in terms of pupil diameter. The presbyopic group showed a 28.5% slower proofreading speed compared with the nonpresbyopic group, whereas their proofreading accuracy was comparable. For both groups, the mean visual fatigue increased significantly during the first 15 min of proofreading, as indicated by a decrease of 0.11 mm in the mean pupil diameter, an increase of 3.8 in the mean bulbar conjunctival redness, and an increase of 9.13 in the mean eye complaint questionnaire score. CONCLUSION: The effect of display curvature was not presbyopia-specific. Low visual fatigue was observed with 1140R and 600R. APPLICATION: Display curvature radii near or in the range of 600R and 1140R and frequent breaks are recommended for both presbyopic and nonpresbyopic groups to reduce their visual fatigue due to visual display terminal tasks.

Determining Ergonomic Smartphone Forms With High Grip Comfort and Attractive Design.

OBJECTIVE: The authors aimed to identify ergonomic smartphone forms by investigating the effects of hand length, four major smartphone dimensions (height, width, thickness, and edge roundness), and smartphone mass on grip comfort and design attractiveness. BACKGROUND: Despite their potential effect on grip comfort and design attractiveness, the dimensions specified above have never been simultaneously considered in a study investigating smartphone gripping. METHOD: Seventy-two young individuals participated in a three-stage study. Stage 1 determined the ranges of the four smartphone dimensions suitable for grip comfort and identified the strengths of their influences. Stage 2 investigated the effects of width and thickness (determined to have the greatest influence) on grip comfort and design attractiveness. Mock-ups of varying masses were fabricated using the dimensions determined during the first two stages to investigate the effect of mass on grip comfort and design attractiveness in Stage 3. RESULTS: Phone width was found to significantly influence grip comfort and design attractiveness, and the dimensions of 140 × 65 (or 70) × 8 × 2.5 mm (height × width × thickness × edge roundness) provided high grip comfort and design attractiveness. The selected dimensions were fit with a mass of 122 g, with masses in the range of 106-137 g being comparable. CONCLUSION: The findings of this study contribute to ergonomic smartphone design developments by specifying dimensions and mass that provide high grip comfort and design attractiveness. APPLICATION: The dimensions and mass determined in this study should be considered for improving smartphone design grip comfort and attractiveness.

The Role of NOX4 in Parkinson's Disease with Dementia.

The neuropathology of Parkinson's disease with dementia (PDD) has been reported to involve heterogeneous and various disease mechanisms. Alpha-synuclein (α-syn) and amyloid beta (Aß) pathology are associated with the cognitive status of PDD, and NADPH oxidase (NOX) is known to affect a variety of cognitive functions. We investigated the effects of NOX on cognitive impairment and on α-syn and Aß expression and aggregation in PDD. In the 6-hydroxydopamine (6-OHDA)-injected mouse model, cognitive and motor function, and the levels of α-syn, Aß, and oligomer A11 after inhibition of NOX4 expression in the hippocampal dentate gyrus (DG) were measured by the Morris water maze, novel object recognition, rotation, and rotarod tests, as well as immunoblotting and immunohistochemistry. After 6-OHDA administration, the death of nigrostriatal dopamine neurons and the expression of α-syn and NOX1 in the substantia nigra were increased, and phosphorylated α-syn, Aß, oligomer A11, and NOX4 were upregulated in the hippocampus. 6-OHDA dose-dependent cognitive impairment was observed, and the increased cognitive impairment, Aß expression, and oligomer A11 production in 6-OHDA-treated mice were suppressed by NOX4 knockdown in the hippocampal DG. Our results suggest that increased expression of NOX4 in the hippocampal DG in the 6-OHDA-treated mouse induces Aß expression and oligomer A11 production, thereby reducing cognitive function.

Sequential Transcriptome Changes in the Penumbra after Ischemic Stroke.

To investigate the changes in the expression of specific genes that occur during the acute-to-chronic post-stroke phase, we identified differentially expressed genes (DEGs) between naive cortical tissues and peri-infarct tissues at 1, 4, and 8 weeks after photothrombotic stroke. The profiles of DEGs were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology analyses, followed by string analysis of the protein-protein interactions (PPI) of the products of these genes. We found 3771, 536, and 533 DEGs at 1, 4, and 8 weeks after stroke, respectively. A marked decrease in biological-process categories, such as brain development and memory, and a decrease in neurotransmitter synaptic and signaling pathways were observed 1 week after stroke. The PPI analysis showed the downregulation of Dlg4, Bdnf, Gria1, Rhoa, Mapk8, and glutamatergic receptors. An increase in biological-process categories, including cell population proliferation, cell adhesion, and inflammatory responses, was detected at 4 and 8 weeks post-stroke. The KEGG pathways of complement and coagulation cascades, phagosomes, antigen processing, and antigen presentation were also altered. CD44, C1, Fcgr2b, Spp1, and Cd74 occupied a prominent position in network analyses. These time-dependent changes in gene profiles reveal the unique pathophysiological characteristics of stroke and suggest new therapeutic targets for this disease.

Where to put the creases? Interactions between hand length, task, screen size, and folding method on the suitability of hand-held foldable display devices.

Limited information is available regarding ergonomic foldable display device forms. This two-stage study involving young South Koreans (divided into three hand-length groups) was conducted to determine ergonomic forms for hand-held foldable display devices considering folding/unfolding comfort and preference. Stage I obtained the suitability of three screen sizes for five tasks. Stage II evaluated 14 different bi- and tri-folding methods considering screen size, folding direction, and folding time. The effects of hand length were all non-significant. Screen size preferences were task-dependent; small screens were preferred for making calls, and medium screens for web searching and gaming. Folding methods affected folding/unfolding comfort and preference; outward screen and Z-shape screen folding were the most preferred bi- and tri-fold concepts, respectively. Screen protection and access appeared to be competing factors in the user preference determination process. Foldable screen size and folding method should be determined by considering tasks, folding/unfolding comfort, and user preferences. Practitioner summary: A 13.5 cm screen was preferred for making calls, whereas a 17.5 cm screen was best for web searching and gaming. An outward bi-fold screen concept with a 17.5 cm screen and Z-shape tri-fold screen concept with a 22.9 cm screen were preferred. Overall, the Z-shape concept was most preferred. Abbreviations: SD: standard deviation; ANOVA: analysis of variance; H: Height; W: Width; T: Thickness.

Protective effect of the imidazoline I2 receptor agonist 2-BFI on oxidative cytotoxicity in astrocytes.

Astrocytes perform a variety of functions that are important for normal neuronal activity and recovery after brain injury. Because astrocytes are very vulnerable to H2O2, protection of astrocytes from oxidative damage in various neurological diseases is important in maintaining brain function and preventing brain damage. In this study, we investigated the characteristics and mechanisms of a specific imidazoline I2 receptor agonist 2-BFI-mediated cytoprotection using a rat astrocyte cultures of H2O2-exposed oxidative stress. Here we show that 2-BFI in H2O2-exposed astrocytes protects cell death through increased lysosomal membrane stability, LC3-II conversion, and subsequently suppresses accumulation of p62. These effects of 2-BFI were significantly reversed after treatment with the lysozyme activity inhibitor Bafilomycin A1. These results suggest that the cytoprotective effects of 2-BFI, which increases lysosomal stability in oxidative stress, may involve regulation of lysosomal-associated membrane protein-dependent autophagy and autolysosome degradation in astrocytes.

Effects of histone acetyltransferase inhibitors on L-DOPA-induced dyskinesia in a murine model of Parkinson's disease.

Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on L-DOPA-induced dyskinesia of Parkinson's disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of L-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model. Anacardic acid 2 mg/kg, garcinol 5 mg/kg, or curcumin 100 mg/kg co-treatment with L-DOPA significantly reduced the axial, limb, and orofacial (ALO) score indicating less dyskinesia with administration of HAT inhibitors in 6-OHDA-lesioned mice. Additionally, L-DOPA's efficacy was not altered by the compounds in the early stage of treatment. The expression levels of c-Fos, Fra-2, and Arc were effectively decreased by administration of HAT inhibitors in the ipsilateral striatum. Our findings indicate that HAT inhibitor co-treatment with L-DOPA may have therapeutic potential for management of L-DOPA-induced dyskinesia in patients with PD.

Hepatocyte SHP deficiency protects mice from acetaminophen-evoked liver injury in a JNK-signaling regulation and GADD45ß-dependent manner.

Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure. Prolonged c-Jun N-terminal kinase (JNK) activation plays a central role in APAP-induced liver injury; however, growth arrest and DNA damage-inducible 45 beta (GADD45ß) is known to inhibit JNK phosphorylation. The orphan nuclear receptor small heterodimer partner (SHP, NR0B2) acts as a transcriptional co-repressor of various genes. The aim of the present study was to investigate the role of SHP in APAP-evoked hepatotoxicity. We used lethal (750 mg/kg) or sublethal (300 mg/kg) doses of APAP-treated wild-type (WT), Shp knockout (Shp-/-), hepatocyte-specific Shp knockout (Shphep-/-), and Shp and Gadd45ß double knockout (Shp-/-Gadd45ß-/-) mice for in vivo studies. Primary mouse hepatocytes were used for a comparative in vitro study. SHP deficiency protected against APAP toxicity with an increased survival rate, decreased liver damage, and inhibition of prolonged hepatic JNK phosphorylation in mice, which was independent of APAP metabolism regulation. Furthermore, Shphep-/- mice showed diminished APAP hepatotoxicity compared with WT mice. SHP-deficient primary mouse hepatocytes also showed decreased cell death and inhibition of sustained JNK phosphorylation following toxic APAP treatment. While SHP expression declined, GADD45ß expression increased after APAP treatment in WT mice. In Shp-/- mice, APAP-evoked GADD45ß induction was significantly enhanced. Notably, the ameliorative effects of SHP deficiency on APAP-induced liver injury were abolished in Shp-/-Gadd45ß-/- mice. The current study is the first to demonstrate that hepatocyte-specific SHP deficiency protects against APAP overdose-evoked hepatotoxicity in a JNK signaling regulation and GADD45ß dependent manner. SHP is suggested to be a novel therapeutic target for APAP overdose treatment.

Medical Procedure-Related Transient Global Amnesia.

BACKGROUND: Transient global amnesia (TGA) is an interesting clinical syndrome characterized by sudden memory loss for recent events and an inability to retain new memories usually lasting several hours and recovering spontaneously. We conducted a literature search of medical procedure-related TGA and its predisposing conditions. METHODS: We performed PubMed searches using the keyword "transient global amnesia" combined with "procedure," "test," "therapy," or various other individual medical procedures. In addition, we described 2 cases of gastroscopy-related TGA. RESULTS: Eighty-nine patients with medical procedure-related TGA in 49 articles were summarized. The most common procedure was cerebral angiography (n = 45), followed by coronary angiography (n = 10) and general anesthesia (n = 9). After categorization, neurological procedures were most common (n = 46, 51.7%), followed by cardiac (n = 17, 19.1%), anesthetic (n = 11, 12.4%), gastrointestinal (n = 4, 4.5%), and pulmonary (n = 2, 2.2%) procedures. CONCLUSIONS: Diverse cases of medical procedure-related TGA have been reported in the literature. Valsalva-associated activities, emotional stress with anxiety, and acute pain were predisposing conditions. An understanding of medical procedure-related TGA may be important for clinicians who perform such medical procedures.

Effect of Inhibition of DNA Methylation Combined with Task-Specific Training on Chronic Stroke Recovery.

To develop new rehabilitation therapies for chronic stroke, this study examined the effectiveness of task-specific training (TST) and TST combined with DNA methyltransferase inhibitor in chronic stroke recovery. Eight weeks after photothrombotic stroke, 5-Aza-2'-deoxycytidine (5-Aza-dC) infusion was done on the contralesional cortex for four weeks, with and without TST. Functional recovery was assessed using the staircase test, the cylinder test, and the modified neurological severity score (mNSS). Axonal plasticity and expression of brain-derived neurotrophic factor (BDNF) were determined in the contralateral motor cortex. TST and TST combined with 5-Aza-dC significantly improved the skilled reaching ability in the staircase test and ameliorated mNSS scores and cylinder test performance. TST and TST with 5-Aza-dC significantly increased the crossing fibers from the contralesional red nucleus, reticular formation in medullar oblongata, and dorsolateral spinal cord. Mature BDNF was significantly upregulated by TST and TST combined with 5-Azd-dC. Functional recovery after chronic stroke may involve axonal plasticity and increased mature BDNF by modulating DNA methylation in the contralesional cortex. Our results suggest that combined therapy to enhance axonal plasticity based on TST and 5-Aza-dC constitutes a promising approach for promoting the recovery of function in the chronic stage of stroke.

Chronic cerebral hypoperfusion induces post-stroke dementia following acute ischemic stroke in rats.

BACKGROUND: Post-stroke dementia (PSD) is one of the major consequences after stroke. Chronic cerebral hypoperfusion (CCH) can induce vascular cognitive impairment and potentiate amyloid pathology. We investigated how CCH contributes to the development of PSD after stroke in the context of neuroinflammation and amyloid pathology. METHODS: We designed a unique animal model for PSD. We performed middle cerebral artery occlusion (MCAO) surgery in rats mimicking acute territorial infarct, which was followed by bilateral common carotid artery occlusion (BCCAo) surgery mimicking CCH. We performed behavioral tests including neurologic function test and water maze task and histological investigations including neuroinflammation, neuronal cell death, amyloid pathology, and aquaporin 4 (AQP4) distribution. RESULTS: Spatial memory was synergistically impaired when BCCAo was superimposed on MCAO. Neuroinflammation with astroglial or microglial activation and amyloid pathology were enhanced in the ipsilateral cortex, thalamus, and hippocampus when BCCAo was superimposed on MCAO. Glymphatic pathway-related AQP4 distribution changed from perivascular to parenchymal pattern. CONCLUSIONS: Our experimental results suggest that CCH may contribute to the development of PSD by interfering with amyloid clearance through the glymphatic pathway and concomitant neuroinflammation. Therapeutic strategy to clear brain metabolic waste through the glymphatic pathway may be a promising approach to prevent PSD after stroke.

A Solution-Processable Liquid-Crystalline Semiconductor for Low-Temperature-Annealed Air-Stable N-Channel Field-Effect Transistors.

A new solution-processable and air-stable liquid-crystalline n-channel organic semiconductor (2,2'-(2,8-bis(5-(2-octyldodecyl)thiophen-2-yl)indeno[1,2-b]fluorene-6,12-diylidene)dimalononitrile, α,ω-2OD-TIFDMT) with donor-acceptor-donor (D-A-D) π conjugation has been designed, synthesized, and fully characterized. The new semiconductor exhibits a low LUMO energy (-4.19 eV) and a narrow optical bandgap (1.35 eV). The typical pseudo-focal-conic fan-shaped texture of a hexagonal columnar liquid-crystalline (LC) phase was observed over a wide temperature range. The spin-coated semiconductor thin films show the formation of large (≈0.5-1 µm) and highly crystalline platelike grains with edge-on molecular orientations. Low-temperature-annealed (50 °C) top-contact/bottom-gate OFETs have provided good electron mobility values as high as 0.11 cm2 (V s)-1 and high Ion /Ioff ratios of 107 to 108 with excellent ambient stability. This indicates an enhancement of two orders of magnitude (100×) when compared with the ß-substituted parent semiconductor, ß-DD-TIFDMT (2,2'-(2,8-bis(3-dodecylthiophen-2-yl)indeno[1,2-b]fluorene-6,12-diylidene)dimalononitrile). The current rational alkyl-chain engineering route offers great advantages for D-A-D π-core coplanarity in addition to maintaining good solubility in organic solvents, and leads to favorable optoelectronic/physicochemical characteristics. These remarkable findings demonstrate that α,ω-2OD-TIFDMT is a promising semiconductor material for the development of n-channel OFETs on flexible plastic substrates and LC-state annealing of the columnar liquid crystals can lower the electron mobility for transistor-type charge transport.

Elevated blood viscosity is associated with cerebral small vessel disease in patients with acute ischemic stroke.

BACKGROUND: Increased level of blood viscosity, which is one of the major factors that determine blood rheology, has been reported as a risk factor or predictor for cerebrovascular events. We investigated how blood viscosity is associated with acute stroke and chronic radiological manifestations of cerebral small vessel disease, and how blood viscosity changes after stroke. METHODS: We prospectively enrolled consecutive patients with acute ischemic stroke. Whole blood viscosities at a low or high shear rate were measured using a scanning capillary tube viscometer, and were referred to as diastolic blood viscosity (DBV) and systolic blood viscosity (SBV), respectively. Correlations between blood viscosity and acute stroke etiology or chronic radiological manifestations of cerebral small vessel disease were investigated. The temporal profiles of blood viscosity at the onset of stroke and follow-up at 1 and 5 weeks were investigated. RESULTS: Of the 127 patients admitted with acute ischemic stroke, 63 patients were included in the final analyses. DBV at the onset of stroke was significantly higher in small artery occlusion (SAO) stroke than in other stroke subtypes (p = 0.037). DBV showed a significant positive correlation with the number of chronic lacunes (r = 0.274, p = 0.030). The temporal profiles of DBV in SAO stroke showed a transient decrease due to the hydration therapy after 1 week and recurrent elevation at 5 week follow-up (p = 0.009). CONCLUSIONS: Our study suggests that elevated DBV may play a role in the development of acute and chronic manifestations of cerebral small vessel disease. The recurring elevation of DBV in SAO stroke indicates that sufficient hydration and additional therapeutic interventions targeting blood viscosity may be needed in patients with SAO stroke.