Penumbra Region Research Articles

Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

Integrated Strategies for Targeting Arteriogenesis and Angiogenesis After Stroke.

The interdependence between arteriogenesis and angiogenesis is crucial for enhancing perfusion by synchronously improving leptomeningeal collaterals (LMCs) and microvascular networks after stroke. However, current approaches often focus on promoting arteriogenesis and angiogenesis separately, neglecting the potential synergistic benefits of targeting both processes simultaneously. Therefore, it is imperative to consider both arteriogenesis and angiogenesis as integral and complementary strategies for post-stroke revascularization. To gain a deeper understanding of their relationships after stroke and to facilitate the development of targeted revascularization strategies, we compared them based on their timescale, space, and pathophysiology. The temporal differences in the occurrence of arteriogenesis and angiogenesis allow them to restore blood flow at different stages after stroke. The spatial differences in the effects of arteriogenesis and angiogenesis enable them to specifically target the ischemic penumbra and core infarct region. Additionally, the endothelial cell, as the primary effector cell in their pathophysiological processes, is promising target for enhancing both. Therefore, we provide an overview of key signals that regulate endothelium-mediated arteriogenesis and angiogenesis. Finally, we summarize current therapeutic strategies that involve these signals to promote both processes after stroke, with the aim of inspiring future therapeutic advances in revascularization.

407: Assessing the fraction of dose originating from the penumbra region for plans of varied complexity

407: Assessing the fraction of dose originating from the penumbra region for plans of varied complexity

The effects and significance of Dicyclopentadiene on the expression of Intersectin-1 after cerebral ischemia-reperfusion in rats

ObjectiveThis study mainly observed the changes in Intersectin-1 (ITSN-1) expression in rat brain tissue after ischemia-reperfusion intervened by Dicyclopentadiene. MethodsSD rats were randomly divided into non-middle Cerebral Artery Occlusion model group (normal group, sham operation group) and Middle Cerebral Artery Occlusion (MCAO) model group [Ischemia reperfusion (cerebral ischemia reperfusion)] reperfusion,IR) (6h, 24h, 72h, 1w, 2w) group, butylphthalein intervention group], First of all, Use Western The expression of ITSN-1 in the cerebral tissue of infarction side after ischemia-reperfusion injury in each group was measured by blotting, and then the loss and degree of nerve function after ischemia-reperfusion injury in each group was evaluated by Zea-Longa scoring method. The morphological changes of cells in the ischemic penumbra region in the normal group and the MCAO model group for 24h were observed by HE staining. Next, 24h was selected as the reperfusion point for intervention with butylphthalein sodium chloride injection. Finally, Zea-Longa scoring method was used to evaluate whether the rats had neurological impairment and its degree, TTC (Triphenyltetrazolium chloride) staining was used to determine whether the rats had cerebral infarction and its extent, and Western The expression of ITSN-1 in the cerebral tissue of infarcted rats after ischemia-reperfusion injury was measured by blotting. Results1. Zea-Longa scoring: Scores, except for the normal group and sham operation group (which scored 0), ranged between 2.75 ± 0.46 in the ischemia-reperfusion 24h group and 1.88 ± 0.35 in the Dicyclopentadiene intervention group, showing statistically significant decreases (P<0.05). 2. HE staining results: The cell structures in the brain tissues of normal group rats were normal with regular nuclear shapes and sizes. There were no obvious abnormal changes. Rats in the ischemia-reperfusion 24h group showed obviously swollen cells, reduced and aggregated nucleus, and cell necrosis in the ischemic penumbra. 3. TTC staining results: Except for the normal group and the sham operation group, which had no infarcts, the ischemia-reperfusion 24h group had the largest volume ratio of cerebral infarction. The volume ratio of cerebral infarction in the Dicyclopentadiene intervention group relatively reduced, making a difference with statistical significance (P<0.05). 4. Western blotting results: After cerebral ischemia-reperfusion in rats, ITSN-1 expression in the infarction-side brain tissue dynamically changed. ITSN-1 expression in the ischemia-reperfusion 24h group was significantly lower among other groups compared to the normal group (P<0.05). After 24 hours, the expression gradually increased after using Dicyclopentadiene intervention, the difference was statistically significant (P<0.05). ConclusionAfter cerebral ischemia-reperfusion in rats, ITSN-1 expression dynamically changed in the infarction-side brain tissue. Dicyclopentadiene can alleviate ischemia-reperfusion injuries in rats, which might be related to the regulation of ITSN-1 expression.

Measurements of low-energy, re-entrant albedo protons by the HEPD-01 space-borne detector

Cosmic rays’ interactions with the residual atmosphere surrounding the Earth produce a variety of particles, like electrons, positrons, protons, anti-protons, and Helium nuclei that can be observed below the local geomagnetic cutoff. In this work, we present new measurements of downward-going, albedo proton fluxes with kinetic energy in the range ∼40–∼250 MeV, performed by the High-Energy Particle Detector (HEPD-01) on board of the China Seismo-Electromagnetic Satellite - CSES-01 - at an altitude of ∼500 km. Employing a dedicated trajectory-tracing simulation routine, the protons collected by HEPD-01 are classified into quasi-trapped (QT), long lifetime (≳10 s) particles concentrating in the equatorial region of the Earth, and un-trapped (UT), distributed at all latitudes; the latter includes both precipitating short lifetime particles (UTS) and pseudo-trapped long lifetime (UTL) populations, abundant in the so-called penumbra regions. The temporal trend of re-entrant protons between 2018 and 2022 is also reported, assessing the stability of such population during the data-taking period of HEPD-01; this highlights their independence from the long-term modulating effect of the solar activity.

Compound Shenma Jingfu granule alleviates cerebral ischemia via HIF-1α-mediated promotion of angiogenesis

BackgroundShenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating cerebral ischemia has not yet been fully elucidated.MethodsAn integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin–eosin (H&E) and Nisslʼs staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting.ResultsIntegrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis.ConclusionSMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical.Graphical

Shikonin attenuates cerebral ischemia/reperfusion injury via inhibiting NOD2/RIP2/NF-κB-mediated microglia polarization and neuroinflammation

ObjectivesMicroglia-mediated neuroinflammation plays a crucial role in the pathophysiological process of multiple neurological disorders such as ischemic stroke, which still lacks effective therapeutic agents. Shikonin possesses anti-inflammatory and neuroprotective properties. However, its underlying mechanism remains elusive. This study aimed to investigate whether Shikonin confers protection against cerebral ischemia/reperfusion (I/R) injury by modulating microglial polarization and elucidate the associated mechanisms. MethodsThis study employed an oxygen-glucose deprivation and reoxygenation (OGD/R) BV2 microglial cellular model and a middle cerebral artery occlusion/reperfusion (MCAO/R) animal model to investigate the protection and underlying mechanism of Shikonin against ischemic stroke. ResultsThe results demonstrated that Shikonin treatment significantly reduced brain infarction volume and improved neurological function in MCAO/R rats. Simultaneously, Shikonin treatment significantly reduced microglial proinflammatory phenotype and levels of proinflammatory markers (inducible-NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6), increased microglial anti-inflammatory phenotype and levels of anti-inflammatory markers (Arginase-1 (Arg1), transforming growth factor-beta (TGF-β), and IL-10), reversed the expression of Nucleotide-binding oligomerization domain 2 (NOD2) and phosphorylation receptor interacting protein 2 (p-RIP2), and suppressed nuclear factor kappa-B (NF-κB) signaling activation in the ischemic penumbra regions. These effects of Shikonin were further corroborated in OGD/R-treated BV2 cells. Furthermore, overexpression of NOD2 markedly attenuated the neuroprotective effects of Shikonin treatment in MCAO/R rats. NOD2 overexpression also attenuated the regulatory effects of Shikonin on neuroinflammation, microglial polarization, and NF-κB signaling activation. ConclusionThis study illustrates that Shikonin mitigates inflammation mediated by microglial proinflammatory polarization by inhibiting the NOD2/RIP2/NF-κB signaling pathway, thereby exerting a protective role. The findings uncover a potential molecular mechanism for Shikonin in treating ischemic stroke.

Dosimetry of Large Field Valencia applicators for Cobalt-60-based brachytherapy.

Non-melanoma skin cancer is one of the most common types of cancer and one of the main approaches is brachytherapy. For small lesions, the treatment of this cancer with brachytherapy can be done with two commercial applicators, one of these is the Large Field Valencia Applicators (LFVA). The aim of this study is to test the capabilities of the LFVA to use clinically 60Co sources instead of the 192Ir ones. This study was designed for the same dwell positions and weights for both sources. The Penelope Monte Carlo code was used to evaluate dose distribution in a water phantom when a 60Co source is considered. The LFVA design and the optimized dwell weights reported for the case of 192Ir are maintained with the only exception of the dwell weight of the central position, that was increased. 2D dose distributions, field flatness, symmetry and the leakage dose distribution around the applicator were calculated. When comparing the dose distributions of both sources, field flatness and symmetry remain unchanged. The only evident difference is an increase of the penumbra regions for all depths when using the 60Co source. Regarding leakage, the maximum dose within the air volume surrounding the applicator is in the order of 20% of the prescription dose for the 60Co source, but it decreases to less than 5% at about 1cm distance. Flatness and symmetry remains unaltered as compared with 192Ir sources, while an increase in leakage has been observed. This proves the feasibility of using the LFVA in a larger range of clinical applications.

Vagus nerve stimulation as a promising neuroprotection for ischemic stroke via α7nAchR-dependent inactivation of microglial NLRP3 inflammasome.

Ischemic stroke is a major cause of disability and death worldwide, and its management requires urgent attention. Previous studies have shown that vagus nerve stimulation (VNS) exerts neuroprotection in ischemic stroke by inhibiting neuroinflammation and apoptosis. In this study, we evaluated the timing for VNS intervention in ischemic stroke, and the underlying mechanisms ofVNS-induced neuroprotection. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. The left vagus nerve at cervical level was exposed and attached to an electrode connected to a low-frequency electrical stimulator. Vagus nerve stimulation (VNS) was given for 60 min before, during and after tMCAO (Pre-VNS, Dur-VNS, Post-VNS). Neurological function was assessed 24 h after reperfusion. We found that all the three VNS significantly protected against the tMCAO-induced injury evidenced by improved neurological function and reduced infarct volume. Moreover, the Pre-VNS was the most effective against the ischemic injury. We found that tMCAO activated microglia in the ischemic core and penumbra regions of the brain, followed by the NLRP3 inflammasome activation-induced neuroinflammation, which finally triggered neuronal death. VNS treatment preserved α7nAChR expression in the penumbra regions, inhibited NLRP3 inflammasome activation and ensuing neuroinflammation, rescuing cerebral neurons. The role of α7nAChR in microglial NLRP3 inflammasome activation in ischemic stroke was further validated using genetic manipulations, including Chrna7 knockout mice and microglial Chrna7 overexpression mice, as well as pharmacological interventions using the α7nAChR inhibitor methyllycaconitine and agonist PNU-282987. Collectively, this study demonstrates the potential of VNS as a safe and effective strategy to treat ischemic stroke, and presents a new approach targeting microglial NLRP3 inflammasome, which might be therapeutic for other inflammation-related diseases.

Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment.

Clinical studies have identified widespread white matter degeneration in ischemic stroke patients. However, contemporary research in stroke has predominately focused on the infarct and periinfarct penumbra regions. The involvement of white matter degeneration after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has remained less explored in experimental models. In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy and quantitative anisotropy at bilateral corpus callosum in diffusion-weighted MRI (DWI) analysis. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. Our study suggests that experimental ischemic stroke induced by MCAO in young rat replicate long-term cognitive impairment and bihemispheric white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID.

Multi-point calorimeter using distributed fiber Bragg gratings for small field dosimetry in radiotherapy.

The interest of using fiber Bragg gratings (FBGs) dosimeters in radiotherapy (RT) lies in their (i) microliter detection volume, (ii) customizable spatial resolution, (iii) multi-point dose measurement, (iv) real-time data acquisition and (v) insensitivity to Cherenkov light. These characteristics could prove very useful for characterizing dose distributions of small and nonstandard fields with high spatialresolution. We developed a multi-point FBGs dosimeter customized for small field RT dosimetry with a spatial resolution of 1mm. The 3cm-long multi-point dosimeter is made by embedding a 80 silica fiber containing an array of thirty (30) co-located 1mm-long fs-written FBGs inside a plastic cylinder with an UV curing optical adhesive. With its higher thermal expansion coefficient, the plastic cylinder increases the sensitivity of the dosimeter by stretching the fiber containing the FBGs when the temperature rises slightly due to radiation energy deposition. Irradiations (2000MU at 600MU/min) were performed with a Varian TrueBeam linearaccelerator. The dose profile of a 2 2cm 6MV beam was measured with a mean relative difference of 1.8% (excluding the penumbra region). The measured output factors for a 6MV beam are in general agreement with the expected values within the experimental uncertainty (except for the 2 2cm field). The detector response to different energy of photon and electron beams is within 5% of the mean response ( pm/Gy). The calorimeter's post-irradiation thermal decay is in agreement with thetheory. An energy-independent small field calorimeter that allows dose profile and output factor measurements for RT using FBGs was developed, which, to our knowledge, has never been done before. This type of detector could prove really useful for small field dosimetry, but also potentially for MRI-LINAC since FBGs are insensitive to magnetic fields and for FLASH since FBGs have been used to measure doses up to100kGy.

Shadow Segmentation With Image Thresholding for Describing the Harshness of Light Sources.

Light sources are usually described by luminous intensity, color temperature and color rendering index, while the harshness of the light source is often overlooked. It is also referred to as the softness or light quality and can be determined by analyzing the shadows it produces. Shadow detection is often addressed in image analysis research, but the methods usually provide solutions for removing shadows. In this research, a method is proposed for isolating shadows from test images, applying thresholding for segmentation of the shadow into umbral and penumbral regions, calculating the shadow metric, and finally calculating the final numerical evaluation of the quality of the light source, i.e., the degree of its softness or harshness. The method proved to be efficient in analyzing halogen, LED and xenon light sources in conjunction with light-shaping attachments that soften the light. The method is not influenced by the intensity of the light source and focuses exclusively on the quality of the light. The method provides a single value to describe this light property and has the potential to become a standardized method for describing the quality of light sources and light-shaping attachments.

Modelling and commissioning validation of eclipse conical cone collimator for stereotactic radiosurgery using Monte Carlo simulation

Abstract Purpose: The miniaturized conical cones for stereotactic radiosurgery (SRS) make it challenging in measurement of dosimetric data needed for commissioning of treatment planning system. This study aims at validating dosimetric characteristics of conical cone collimator manufactured by Varian using Monte Carlo (MC) simulation technique. Methods &amp; Material: Percentage depth dose (PDD), tissue maximum ratio (TMR), lateral dose profile (LDP) and output factor (OF) were measured for cones with diameters of 5mm, 7·5mm, 10mm, 12·5 mm, 15 mm and 17·5 mm using EDGE detector for 6MV flattening filter-free (FFF) beam from Truebeam linac. Similarly, MC modelling of linac for 6MVFFF beam and simulation of conical cones were performed in PRIMO. Subsequently, measured beam data were validated by comparing them with results obtained from MC simulation. Results: The measured and MC-simulated PDDs or TMRs showed close agreement within 3% except for cone of 5mm diameter. Deviations between measured and simulated PDDs or TMRs were substantially higher for 5mm cone. The maximum deviations at depth of 10cm, 20cm and at range of 50% dose were found 4·05%, 7·52%, 5·52% for PDD and 4·04%, 7·03%, 5·23% for TMR with 5mm cone, respectively. The measured LDPs acquired for all the cones showed close agreement with MC LDPs except in penumbra region around 80% and 20% dose profile. Measured and MC full-width half maxima of dose profiles agreed with nominal cone size within ± 0·2 mm. Measured and MC OFs showed excellent agreement for cone sizes ≥10 mm. However, deviation consistently increases as the size of the cone gets smaller. Findings: MC model of conical cones for SRS has been presented and validated. Very good agreement was found between experimentally measured and MC-simulated data. The dosimetry dataset obtained in this study validated using MC model may be used to benchmark beam data measured for commissioning of SRS for cone planning.

Classification of circular polarization Stokes profiles in a sunspot using k-means clustering

The magnetic and velocity fields in sunspots are highly structured on small spatial scales which are encoded in the Stokes profiles. The Stokes profiles are in turn, derived from a sequence of polarization modulations on the incoming light that are imaged using an analyser-detector combination. Our aim is to identify Stokes profiles in a sunspot which exhibit spectral characteristics that deviate from those associated with the Evershed flow and their corresponding spatial distribution. To that end, we employ the k-means clustering routine to classify Stokes V spectra in the penumbra of a regular, unipolar sunspot, that also comprises a granular and a filamentary light bridge. We find that 75% of the penumbral region, corresponding to about 93500 pixels, is dominated by profiles comprising two, nearly anti-symmetric lobes, while 21% of the area is occupied by three-lobed profiles that are associated with the Evershed flow returning to the solar photosphere. The remaining 4% of the penumbral area is dominated by four groups/families of profiles - Group 1: three-lobed profiles in which both the rest and strong downflowing (sometimes supersonic) component have the same polarity as the host sunspot and seen exclusively in the filamentary light bridge. Group 2: single, red-lobed profiles occupying an area of about 2% located at the outer penumbra in discrete patches that possibly signify the downflowing leg of an Ω-loop. Group 3: three-lobed or highly asymmetric profiles, in which the rest component and the strong downflowing component have an opposite polarity as the sunspot. These occupy about 1.4% of the penumbra’s area and are seen in conspicuous, elongated structures or isolated patches in the outer penumbra and at the penumbra-quiet Sun boundary. Group 4: three lobed-profiles, in which the rest component has the same polarity as the sunspot and a weaker, upflowing component with a polarity opposite that of the sunspot. These profiles are located close to the entrance of the filamentary light bridge and are found in only 0.12% of the penumbral area. These minority groups of profiles could be related to dynamic phenomena that could also affect the overlying chromosphere. The simplicity and speed of k-means can be utilized to identify such anomalous profiles in larger data sets to ascertain their temporal evolution and the physical processes responsible for these inhomogeneities.

Single-Cell Multiome Analysis Reveals Neuroprotection by Elovanoids in Experimental Ischemic Stroke

Ischemic stroke results in severe loss of neurological functions, and a large proportion of survivors display the onset of cognitive impairments. Administration of a novel class of very long-chain polyunsaturated fatty acids (VLC-PUFAs) termed elovanoids (ELV-N34) or its VLC-PUFA precursor (C34:6) are protective against both in vitro and in vivo models of uncompensated oxidative stress and ischemic stress. We found that ELV-N34 or C34:6 delivery attenuates sensorimotor deficits after ischemic stroke. Furthermore, we uncovered that ELV and its precursors protect against ischemic damage by modulating inflammatory signaling and increasing the expression of neuroprotective genes. We used 10X Single Cell Multiome (ATAC + Gene Expression) to compare genomic and epigenomic responses in naïve rats and after experimental ischemic treatment. Adult Sprague-Dawley rats underwent 2 hours of middle cerebral artery occlusion (MCAo) via intraluminal suture. Rats received vehicle, ELV-N34, or C34:6 delivered intranasally 1 hour, 1 day, and 2 days after 2 hours of MCAo. Brains were harvested on day 3 from the ipsilesional cortex (penumbra region) and subcortex. Nuclei were isolated and processed according to 10X Genomics Single Cell Multiome protocol. ELV-N34 or C34:6 treatment reduced neurological deficits after MCAo. Joint single-cell analysis revealed increases in microglia and leukocyte abundance as well as a loss of neuronal populations after MCAo. Differential gene expression revealed that ELV or its precursors protected against MCAo through complex mechanisms involving anti- inflammatory signaling and promoted neuroregeneration in microglia, astrocytes, neurons, and other neural cells. ELV/precursors exert their bioactivity by modulating conversion to neuroprotective cell phenotypes in neurodegenerative diseases such as stroke or Alzheimer's disease.

Immune pathway activation in neurons triggers neural damage after stroke

Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4h and 1, 3, and 7days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-binding protein β (C/EBPβ). To our surprise, the canonical inflammatory cytokine gene targets for C/EBPβ, including interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBPβ or IL-1β and TNF-α substantially alleviates downstream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury.

Identification of Novel Circular RNA Targets in Key Penumbra Region of Rats After Cerebral Ischemia-Reperfusion Injury

Circular RNAs (circRNAs) are abundantly and stably expressed in the brain of mammals and humans. Some circRNAs are implicated in ischemic stroke. Therefore, we aimed to detect how circRNAs change in the key penumbra area during cerebral ischemia-reperfusion (CI/R) injury. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), during which the permanent blocking period was 2 h and reperfusion time was 24 or 72 h. Then modified neurologic severity score (mNSS), triphenyl tetrazolium chloride (TTC) staining and HE staining were used to exhibiting damage between rats in different groups. The penumbra regions of all rats were dissected and total RNA was further processed for high-throughput sequencing. CircRNA expression profiles were screened and bioinformatics analyses were conducted to investigate these differentially expressed circRNAs. Some of them were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the establishment of a circRNA-miRNA-mRNA network and the detection of their downstream molecules. A total of 99 and 98 circRNAs were differentially expressed at CI/R 24 h and CI/R 72 h, respectively. Notably, 21 circRNAs significantly changed at both reperfusion points. Three circRNAs, namely circ.7225, circ.5415, and circ.20623 were found to be associated with CI/R injury and might be preferred targets. Common downstream miR-298-5p and Bcl-3 were found to make up the circRNA-miRNA-mRNA network. Novel circRNA targets came to light in the penumbra of rats during CI/R injury and might establish the circRNA-miRNA-mRNA relationship, thus serving as potential biomarkers for ischemic stroke treatment.

Progression of reactive gliosis and astroglial phenotypic changes following stab wound-induced traumatic brain injury in mice.

Astrocytes are the main homeostatic cells in the central nervous system (CNS) and they have an essential role in preserving neuronal physiology. After brain injury, astrocytes become reactive, and that involves a profound change in the astroglial gene expression program as well as intense cytoskeleton remodeling that has been classically shown by the up-regulation of glial fibrillary acidic protein (GFAP), a pan-reactive gene over-expressed in reactive astrocytes, independently of the type of injury. Using the stab wound rodent model of penetrating traumatic injury in the cortex, we here studied the reactive astroglial morphology and reactive microgliosis in detail at 1, 3, 7, 14, and 28 days post-injury (dpi). By combining immunohistochemistry, morphometrical parameters, and Sholl analysis, we segmented the astroglial cell population into clusters of reactive astrocytes that were localized in the core, penumbra, and distal regions of the stab wound. Specifically, highly reactive clusters with more complex morphology, increased C3, decreased aquaporin-4 (AQP4), and glutamine synthetase (GS) expression, were enriched at 7 dpi when behavioral alterations, microgliosis, and neuronal alterations in injured mice were most significant. While pro-inflammatory gain of function with peripheral lipopolysaccharide (LPS) administration immediately after a stab wound expanded these highly reactive astroglial clusters, the treatment with the NF-κB inhibitor sulfasalazine reduced the abundance of this highly reactive cluster. Increased neuronal loss and exacerbated reactive microgliosis at 7 dpi were associated with the expansion of the highly reactive astroglial cluster. We conclude that highly reactive astrocytes found in stab wound injury, but expanded in pro-inflammatory conditions, are a population of astrocytes that become engaged in pathological remodeling with a pro-inflammatory gain of function and loss of homeostatic capacity. Controlling this astroglial population may be a tempting strategy to reduce neuronal loss and neuroinflammation in the injured brain.

Analysis of photospheric magnetic fields in AR 12546: a case study

We investigate high-resolution observations with the spectropolarimeter (SP) aboard the Hinode satellite of the Solar Optical Telescope (SOT) of a positive polarity sunspot of an active region (AR) (NOAA 12546). We present a case study for the properties of the thermal, magnetic field, and plasma flows as a function of the optical depth from the inversion of the observed Stokes profiles, covering a wide field of view area. Particular attention is paid to the examination of the net circular polarization (NCP) and area asymmetry of spectral lines in sunspots. We detect a large red-shifted velocity of 10 km sec−1 localized with the presence of a strong magnetic field corresponding to the NCP best fit of the inverted profiles. In addition, the comparison between the observed and calculated NCPs or Stokes V area asymmetries of spectral lines fitted well for most pixels in the field of view region, with a significant indication of a single-component inversion. We study the vertical gradients of temperature, magnetic strength, inclination field, and LOS velocity in the deeper and higher layers of the photosphere. The difference in the penumbral temperature between the two atmospheric layers is −130 K. The penumbral regions reveal a magnetic field gradient of Delta B sim -0.5 to −0.9 G km−1. The inclination gradient in the limb-side penumbra is between (Delta gamma /Delta z) = -9 times 10^{-3} deg km−1 to -3.5 times 10^{-2} deg km−1. In particular, we find a higher positive inclination gradient in the disk center-side penumbra (Delta gamma /Delta z)= 0.2 - 1.5 deg text{ km}^{-1}. The velocity gradient is (Delta V_{LOS}/Delta log tau )= -0.13 to −0.30 km sec−1 in the limb-side penumbra, and the disk center-side penumbra is given by (Delta V_{LOS}/Delta log tau )= 0.11 to 0.29 km sec−1.

Reduction of scan duration and radiation dose in cerebral CT perfusion imaging of acute stroke using a recurrent neural network

Objective. Cerebral CT perfusion (CTP) imaging is most commonly used to diagnose acute ischaemic stroke and support treatment decisions. Shortening CTP scan duration is desirable to reduce the accumulated radiation dose and the risk of patient head movement. In this study, we present a novel application of a stochastic adversarial video prediction approach to reduce CTP imaging acquisition time. Approach. A variational autoencoder and generative adversarial network (VAE-GAN) were implemented in a recurrent framework in three scenarios: to predict the last 8 (24 s), 13 (31.5 s) and 18 (39 s) image frames of the CTP acquisition from the first 25 (36 s), 20 (28.5 s) and 15 (21 s) acquired frames, respectively. The model was trained using 65 stroke cases and tested on 10 unseen cases. Predicted frames were assessed against ground-truth in terms of image quality and haemodynamic maps, bolus shape characteristics and volumetric analysis of lesions. Main results. In all three prediction scenarios, the mean percentage error between the area, full-width-at-half-maximum and maximum enhancement of the predicted and ground-truth bolus curve was less than 4 ± 4%. The best peak signal-to-noise ratio and structural similarity of predicted haemodynamic maps was obtained for cerebral blood volume followed (in order) by cerebral blood flow, mean transit time and time to peak. For the 3 prediction scenarios, average volumetric error of the lesion was overestimated by 7%–15%, 11%–28% and 7%–22% for the infarct, penumbra and hypo-perfused regions, respectively, and the corresponding spatial agreement for these regions was 67%–76%, 76%–86% and 83%–92%. Significance. This study suggests that a recurrent VAE-GAN could potentially be used to predict a portion of CTP frames from truncated acquisitions, preserving the majority of clinical content in the images, and potentially reducing the scan duration and radiation dose simultaneously by 65% and 54.5%, respectively.