Interpretations of galactic center gamma-ray excess confronting the PandaX-II constraints on dark matter-neutron spin-dependent scatterings in the NMSSM

The Weakly Interacting Massive Particle (WIMP) has been one of the most attractive candidates for Dark Matter (DM), and the lightest neutralino ($\widetilde{\chi}^0_1$) in the Next-to-Minimal Supersymmetric Standard Model (NMSSM) is an interesting realization of WIMP. The Galactic Center Excess (GCE) can be explained by WIMP DM annihilations in the sky. In this work we consider the $Z_3$-NMSSM where the singlet $S$ and Singlino $\widetilde{S}^0$ components play important roles in the Higgs and DM sector. Guided by our analytical arguments, we perform a numerical scan over the NMSSM parameter space for the GCE explanation by considering various observables such as the Standard Model (SM) Higgs data measured by the ATLAS and CMS experiments, and the $B$-physics observables $BR(B_s\rightarrow X_s\gamma)$ and $BR(B_s\rightarrow \mu^+\mu^-)$. We find that the correlation between the coupling $C_{A_1 b\bar{b}}$ in $\langle \sigma_{b\bar{b}} v \rangle _{0}$ and the coupling $C_{Z \widetilde{\chi}^0_1 \widetilde{\chi}^0_1}$ in DM-neutron Spin Dependent (SD) scattering rate $\sigma^{SD}_{\widetilde{\chi}^0_1-N}$ makes all samples we obtain for GCE explanation get excluded by the PandaX-II results. Although the DM resonant annihilation scenarios may be beyond the reach of our analytical approximations and scan strategy, the aforementioned correlation can be a reasonable motivation for future experiments such as PandaX-nT to further test the NMSSM interpretation of GCE.Comment: 11 pages, 4 figures, meeting the published version by EPJ

In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia

The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5-2.0 × 107 /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance

A unique stroke case with contralateral sulcal hyperintensity on fluid-attenuated inversion recovery image changed to linear serpiginous structures

An 83-year-old man developed acute ischemic stroke. Brain magnetic resonance imaging (MRI) showed ischemic stroke in the left parietal lobe gyri, but fluid-attenuated inversion recovery (FLAIR) showed hyperintensity in the contralateral right temporal-occipital lobe sulci. Follow-up FLAIR image showed the gradual disappearance of the sulcal hyperintensity in the sulci and changed to linear serpiginous structures. This is a unique stroke case showing transitioned FLAIR findings suggesting that the sulcal hyperintensity findings are more severe and an earlier ischemic condition than the linear serpiginous structures

In vivo imaging of autophagy in a mouse stroke model

Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 light chain 3 (LC3) transgenic (Tg) mice, in vivo imaging of autophagy was performed at 1, 3 and 6 d after 60 min transient middle cerebral artery occlusion (tMCAO). Ex vivo imaging of autophagy, testing of the autophagy inhibitor 3-methyladenine (3-MA), estern blot analysis, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and fluorescent analyses were performed on brain sections following tMCAO. In vivo fluorescent signals were detected above the ischemic hemisphere through the skull bone at 1, 3 and 6 d after tMCAO, with a peak at 1 d. Similar results were obtained with ex vivo fluorescence imaging. western blot analysis revealed maximum LC3-I and LC3-II expression at 1 d after tMCAO and fluorescence immunohistochemistry demonstrated that GFP-LC3-positive cells were primarily neuronal, not astroglial or microglial, cells. The number of GFP-LC3/TUNEL double-positive cells was greater in the peri-ischemic area than in the core. These results provided evidence of in vivo autophagy detection, with a peak at 1 d, in a live animal model following cerebral ischemia. This novel technique could be valuable for monitoring autophagic processes in vivo in live stroke patients, as well as for clarifying the detailed role of autophagy in the ischemic brain, as well as in other neurological diseases

Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion

BACKGROUND: Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood. METHODS: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry. RESULTS: In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress. CONCLUSIONS: The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion

Multi‐modal combination therapy rescued a frequent ischemic stroke patient due to giant cell arteritis

Ischemic stroke (IS) due to giant cell arteritis (GCA) is rare, but highly mortal. Here, we report a 72-year-old man who showed frequent IS with GCA. Initial therapy with prednisolone increased the frequency of IS, which disappeared after continuous multi-modal combination therapy with corticosteroids, immunosuppressive agents, antiplatelets, and statin. The present case was discharged with independent walk, suggesting that a multi-modal combination therapy rescued the GCA patient from frequent IS

Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion

BACKGROUND: The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and α-synuclein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX). METHODS: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry. RESULTS: The present study revealed that the expressions of phospho-tau and phospho-α-synuclein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P CONCLUSIONS: Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH

Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model

Alzheimer's disease (AD) is the most common dementia and a progressive neurodegenerative disorder aggravated by chronic hypoperfusion (HP). Since numerous evidence suggests that inflammation is related with AD pathology, we investigated the expression change of two anti-inflammatory markers, inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and alpha-2-HS-glycoprotein (AHSG), in a novel AD model (APP23) with HP at 12 month of age. As compared with wild type (WT, n = 10), immunohistochemical analysis showed a higher ITIH4 and a lower AHSG expressions in the cerebral cortex, hippocampus, and thalamus of the APP23 + HP group (n = 12) than the simple APP23 (n = 10) group (*p < 0.05 and **p < 0.01 versus WT; #p < 0.05 and # #p < 0.01 versus APP23). The present study provides an upregulation of anti-inflammatory ITIH4 and a downregulation of pro-inflammatory TNFα-dependent AHSG in a novel AD plus HP mice model

Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis

Oxidative stress is associated with the degeneration of both motor neurons and skeletal muscles in amyotrophic lateral sclerosis (ALS). A free radical scavenger edaravone has been proven as a therapeutic drug for ALS patients, but the neuroprotective mechanism for the oxidative stress of ALS has not been fully investigated. In this study, we investigated oxidative stress in ALS model mice bearing both oxidative stress sensor nuclear erythroid 2-related factor 2 (Nrf2) and G93A-human Cu/Zn superoxide dismutase (Nrf2/G93A) treated by edaravone. In vivo Nrf2 imaging analysis showed the accelerated oxidative stress both in spinal motor neurons and lower limb muscles of Nrf2/G93A mice according to disease progression in addition to the enhancement of serum oxidative stress marker dROMS. These were significantly alleviated by edaravone treatment accompanied by clinical improvements (rotarod test). The present study suggests that in vivo optical imaging of Nrf2 is useful for detecting oxidative stress in ALS, and edaravone alleviates the degeneration of both motor neurons and muscles related to oxidative stress in ALS patients