4-Hydroxyl-2-Nonenal Localized Expression Pattern in Retrieved Clots is Associated with Large Artery Atherosclerosis in Stroke Patients.

OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).

Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model.

Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke that could cause hemorrhagic complications. We aimed to evaluate the pathology of MT-induced arterial damage and neurovascular unit (NVU) disruption in relation to tissue-type plasminogen activator (tPA) injection for acute ischemic stroke. We induced transient middle cerebral artery occlusion in male SHR/Izm rats for 2 hr. This was followed by reperfusion with/without tPA (3 mg/kg) and "rough suture" insertion that mimicked MT once or thrice (MT1 or MT3). Compared with the control group, the tPA + MT3 group presented with an increase in the cerebral infarct and hemorrhage with severer IgG leakage. Moreover, structural damage reaching the tunica media was detected in the MT3 and tPA + MT3 groups. The tPA + MT3 group presented with increased matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression with some MMP9-positive cells expressing a neutrophil marker myeloperoxidase. Furthermore, basal lamina detachment from astrocyte foot processes was observed in the tPA + MT1 and tPA + MT3 groups. These findings suggest that MT causes direct arterial damage, as well as VEGF and MMP9 upregulation, which results in NVU disruption and hemorrhagic complications in acute ischemic stroke, especially when combined with tPA.

Antioxidative effects of a novel dietary supplement Neumentix in a mouse stroke model.

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.

Bone Marrow Stromal Cell Transplantation Drives Molecular Switch from Autophagy to the Ubiquitin-Proteasome System in Ischemic Stroke Mice.

BACKGROUND: Bone marrow stromal cell (BMSC) transplantation is a promising therapeutic approach for cerebral ischemia, as it elicits multiple neuroprotective effects. However, it remains unclear how BMSC transplantation modulates the ubiquitin-proteasome system (UPS) and autophagy under cerebral ischemia. METHODS: In the present study, an intermediate level of cerebral ischemia (30 minutes) was chosen to examine the effect of BMSC transplantation on the molecular switch regulating UPS and autophagy. BMSC or vehicle was stereotactically injected into the penumbra 15 minutes after sham operation or transient middle cerebral artery occlusion (tMCAO). RESULTS: Thirty minutes of tMCAO artery occlusion significantly increased TUNEL-, ubiquitin-, and p62-positive cells (which peaked at 72 hours, 2 hours, and 2 hours after reperfusion, respectively) and ratios of both BAG3/BAG1 and LC3-II/LC3-I at 24 hours after reperfusion. However, intracerebral injection of BMSCs significantly reduced infarct volume and numbers of TUNEL- and p62-positive cells, and improved BAG3/BAG1 and LC3-II/LC3-I ratios. In addition, observed increases in ubiquitin-positive cells 2 hours after reperfusion were slightly suppressed by BMSC transplantation. CONCLUSIONS: These data suggest a protective role of BMSC transplantation, which drove the molecular switch from autophagy to UPS in a murine model of ischemic stroke.

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.

A Unique Recurrent Stroke Case due to Bilateral Vertebral Artery Dissection with Familial Hirschsprung Disease.

Vertebral artery (VA) dissection is one major cause of brain infarction in young and middle-aged adults. Risk factors for VA dissection are hypertension, diabetes mellitus, hyperlipidemia, trauma, and genetic factors. A 32-year-old man with familial Hirschsprung disease at the age of 2 presented cerebellar ischemic stroke due to bilateral VA dissections. A stroke recurred within 17 days despite oral dual antiplatelet therapy. Bilateral VA dissections and recurrent dissections are related to genetic mutations associated with connective tissue diseases. A part of familial Hirschsprung disease has genetic factors in common with cerebrovascular disease. There may be a common genetic background between his VA dissection and Hirschsprung disease.

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 < .05 and ⁎⁎P < .01 versus WT; #P < .05 and ##P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (⁎⁎P < .01 versus WT; #P < .05, and ##P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/day, from 4.5 to 12 months) significantly reduced tau and α-synuclein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group. 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.

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-ß 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-ß 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-ß 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.

Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling.

Stachybotrys microspora triprenyl phenol (SMTP)-44D has both anti-oxidative and anti-inflammatory activities, but its efficacy has not been proved in relation to the pathological changes of neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) in ischemic stroke. Here, the present study was designed to assess the efficacies of SMTP-44D, moreover, compared with the standard neuroprotective reagent edaravone in ischemic brains. ICR mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, SMTP-44D (10 mg/kg) or edaravone (3 mg/kg) was intravenously administrated through subclavian vein just after the reperfusion, and these mice were examined at 1, 3, and 7 d after reperfusion. Compared with the vehicle group, SMTP-44D treatment revealed obvious ameliorations in clinical scores and infarct volume, meanwhile, markedly suppressed the accumulations of 4-HNE, 8-OHdG, nitrotyrosine, RAGE, TNF-α, Iba-1, and cleaved caspase-3 after tMCAO. In addition, SMTP-44D significantly prevented the dissociation of NVU and improved the intensity of NAGO/BDNF and the number of BDNF/TrkB and BDNF/NeuN double positive cells. These effects of SMTP-44D in reducing oxidative and inflammatory stresses were similar to or stronger than those of edaravone. The present study demonstrated that SMTP-44D showed strong anti-oxidative, anti-inflammatory, and anti-apoptotic effects, moreover, the drug also significantly improved the NVU damage and NVTC in the ischemic brain.

Reduction of Ischemia Reperfusion-Related Brain Hemorrhage by Stachybotrys Microspora Triprenyl Phenol-7 in Mice With Antioxidant Effects.

BACKGROUND: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both thrombolytic and anti-inflammatory effects, but its neuroprotective effects on cerebral ischemia are still unclear. The present study assessed the antioxidative and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle cerebral artery occlusion (tMCAO) mice. METHODS: After 60 minutes tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the hemorrhage and expressive changes of antioxidative markers in brains. RESULTS: SMTP-7 treatment showed a similar antithrombotic effect to tPA, but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage volumes nor showed NVU protective effect. CONCLUSIONS: The present study suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.

Neuroprotective Effects of Tocovid Pretreatment in a Mouse Stroke Model.

BACKGROUND: Tocovid is a new combination of tocotrienols and tocopherol, both of which are neuroprotective agents for preventing cerebral infarction in mice. However, the effects of tocovid on anti-inflammation in ischemic model remain elusive. In the present study, we assessed the effects of Tocovid pretreatment on anti-inflammatory effects after transient middle cerebral occlusion (tMCAO) in mice. MATERIALS AND METHODS: We evaluated the therapeutic and anti-inflammatory effects of tocovid pretreatment (200 mg/kg per day, for 1 month) on mice brain under 60 minutes of tMCAO. The expressive changes of inflammatory markers were observed after tMCAO in mice. RESULTS: Tocovid pretreatment greatly improved the mice neurobehaviors, reduced infarct volumes and decreased expressions of inflammatory markers such as tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and ionized calcium binding adapter molecule-1 (Iba-1), and improved the damage of neurovascular units including matrix metallopeptidase 9, IgG and collagen IV after tMCAO. CONCLUSIONS: Our present findings demonstrated that oral tocovid pretreatment showed obviously neuroprotective and at least in part by anti-inflammatory effects in ischemic mice brain.

Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain.

BACKGROUND: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. MATERIALS AND METHODS: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. RESULTS: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. CONCLUSIONS: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

Antineuroinflammatory Effect of SMTP-7 in Ischemic Mice.

BACKGROUND: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both potentials of thrombolytic and neuroprotective effects, but its detailed neuroprotective mechanisms in ischemic stroke are still unclear. Here, we assessed the neuroprotective effects of SMTP-7 for anti-inflammatory and antiapoptosis mechanisms after 60 minutes of transient middle cerebral artery occlusion (tMCAO) in mice. METHODS: After 60minutes of tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA+SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24hours after reperfusion. We histologically assessed the antineuroinflammatory effect of SMTP-7 on the expressive changes of inflammatory markers in ischemic mouse brains. RESULTS: Compared with the vehicle and tPA groups, SMTP-7 treatment significantly improved clinical scores and decreased the infarct volume and the numbers of TNF-α, nuclear factor-κB (NF-κB), nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and cleaved caspase-3-positive cells in the brain of mice at 24hours after tMCAO but not p62-positive cells. However, tPA+SMTP-7 treatment did not show such effects. CONCLUSIONS: The present study suggested that SMTP-7 provides a therapeutic benefit for ischemic stroke mice through anti-inflammatory and antiapoptotic effects but not antiautophagic effect.

Different Characteristics of Anterior and Posterior Branch Atheromatous Diseases with or without Early Neurologic Deterioration.

BACKGROUND: Among several types of ischemic stroke (IS), branch atheromatous disease (BAD) is known to be the leading cause of disability. METHODS: A total of 1919 patients with acute IS were retrospectively analyzed, and BAD patients were classified into anterior or posterior BAD, depending on the responsible vascular territories. These patients were further subcategorized with or without early neurologic deterioration (END or no-END). RESULTS: Of all IS patients, 14.3% had BAD, and 202 patients (73.7%) were further classified as anterior BAD and 72 patients (26.3%) as posterior BAD. The prevalence of diabetes mellitus and END was significantly higher in posterior than in anterior BAD (44.4% vs 26.4%, P < .01; 18.1% vs 5.4%, P < .01, respectively). Posterior BAD showed a higher proportion of female patients and an older age (69.2% vs 39.0%, P < .05; 79.1 ± 7.7 vs 70.5 ± 10.7, P < .01, respectively) in END than in no-END. The modified Rankin Scale was worse in posterior BAD at 90 days (2.5 ± 1.6, P < .01) than in anterior BAD (1.6 ± 1.4). CONCLUSIONS: Our present study shows that posterior BAD is a worse clinical outcome than anterior BAD, with more vascular risk factors. Older female patients with posterior BAD showed a higher risk of END, leading to a worse clinical outcome.

Neuroprotective Effects of a Novel Antioxidant Mixture Twendee X in Mouse Stroke Model.

BACKGROUND: Oxidative stress and inflammation are important aggravating factors in acute ischemic stroke. METHODS: In the present study, the neuroprotective effects of a novel antioxidant mixture Twendee X containing multiple antioxidative ingredients, such as coenzyme Q10, ascorbic acid, and cystine, were evaluated. After the pretreatment of a vehicle or Twendee X (20 mg/kg/d) for 14 days, mice were subjected to transient middle cerebral artery occlusion for 60 minutes and further treated with vehicle or Twendee X for 1 or 5 days. RESULTS: Twendee X administration reduced the infarct size, and reduced oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine, 4-hydroxy-2-nonenal, and Nε-(carboxymethyl) lysine (one of advanced glycation end products), as well as inflammatory markers such as ionized calcium binding adapter molecule-1, tumor necrosis factor-α, and monocyte chemotactic protein-1. CONCLUSIONS: In the present study, the neuroprotective effects of Twendee X were shown on transient middle cerebral artery occlusion mice via antioxidative and anti-inflammatory pathways, providing a potential of Twendee X as one preventive and therapeutic treatment.

Comparative Gait Analysis in Progressive Supranuclear Palsy and Parkinson's Disease.

BACKGROUND: Although changes to gait are an important clinical feature of progressive supranuclear palsy (PSP), systematic analyses have not been well examined, especially in comparison to Parkinson's disease (PD). METHODS: The characteristics of gait in 20 PSP patients (14 males and 6 females) were evaluated in comparison to 124 PD patients (64 males and 60 females) and 24 controls, that is, healthy age-matched adults (5 males and 19 females). Gait in patients was recorded in a 10-m walking test at a self-selected speed. During this time, patients felt most comfortable while wearing a new portable triaxial accelerometer rhythmogram device. Gait variables among the 3 groups were compared. RESULTS: Both PSP and PD patients shared the following similar hypokinetic gait characteristics: decreased velocity, step length, cadence and mean acceleration. Step time and variability in step time were mutually related. However, among the 3 groups, PSP patients showed characteristically low vertical displacement and a higher acceleration than PD patients at the same cadence. CONCLUSION: Although PSP and PD patients showed similar hypokinetic gait, a reduced vertical displacement characterized walking in PSP patients, differing substantially from the characteristics of walking displayed by PD patients.

Temporal Profiles of Stress Protein Inductions after Focal Transient Ischemia in Mice Brain.

BACKGROUND: Stress proteins have been found to play important protective roles against ischemic brain injury under hypoxic, oxidative, heat shock, and proteasome stresses. METHODS: In the present study, we investigated the temporal profiles of the major stress proteins including hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), heat shock protein 72 (HSP72), constitutive heat shock cognate protein 73 (HSC73), and ubiquitin after 45 minutes of transient middle cerebral artery occlusion (tMCAO) in the mice brain up to 7 days after reperfusion. RESULTS: Immunohistochemical analyses of HIF-1α, GSH, HSP72, and ubiquitin showed little immunoreactivity of neural cells in sham control brain, whereas HSC73 showed a constitutive immunoreactivity. After tMCAO, HSC73 showed the fastest increase at 12 hours in the peri-ischemic area, followed by HIF-1α with a peak at 24 hours, GSH, HSP72, and ubiquitin with a peak at 72 hours. All these stress proteins returned toward the baseline levels until 7 days. In the ischemic core, these stress proteins showed a similar change with less reaction compared to the peri-ischemic area. CONCLUSIONS: These data showed temporal expressions of HIF-1α, GSH, HSP72, HSC73, and ubiquitin in the mice brain after tMCAO, which might provide a better understanding of neuroprotective mechanisms and novel targets for therapeutic intervention of brain ischemic disease.

Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia.

The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 × 1011 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia.

Protective effect of scallop-derived plasmalogen against vascular dysfunction, via the pSTAT3/PIM1/NFATc1 axis, in a novel mouse model of Alzheimer's disease with cerebral hypoperfusion.

A strong relationship between Alzheimer's disease (AD) and vascular dysfunction has been the focus of increasing attention in aging societies. In the present study, we examined the long-term effect of scallop-derived plasmalogen (sPlas) on vascular remodeling-related proteins in the brain of an AD with cerebral hypoperfusion (HP) mouse model. We demonstrated, for the first time, that cerebral HP activated the axis of the receptor for advanced glycation endproducts (RAGE)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/provirus integration site for Moloney murine leukemia virus 1 (PIM1)/nuclear factor of activated T cells 1 (NFATc1), accounting for such cerebral vascular remodeling. Moreover, we also found that cerebral HP accelerated pSTAT3-mediated astrogliosis and activation of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, probably leading to cognitive decline. On the other hand, sPlas treatment attenuated the activation of the pSTAT3/PIM1/NFATc1 axis independent of RAGE and significantly suppressed NLRP3 inflammasome activation, demonstrating the beneficial effect on AD.

Actual Telemedicine Needs of Japanese Patients with Neurological Disorders in the COVID-19 Pandemic.

Objective During the coronavirus disease 2019 (COVID-19) pandemic, many social activities have moved online using applications for digital devices (e.g. computers, smartphones). We investigated the needs of telemedicine and trends in medical status and social care situations of Japanese patients with neurological disorders in order to estimate their affinity for an online telemedicine application. Methods We designed an original questionnaire for the present study that asked participants what problems they had with hospital visits, how the COVID-19 pandemic had affected their lives, and whether or not they would like to receive telemedicine. Patients The present study included volunteer caregivers, participants with Parkinson's disease (PD), epilepsy, stroke, dementia, immune-mediated neurological disease (IMMD), spinocerebellar degeneration (SCD), amyotrophic lateral sclerosis (ALS), headache, myopathy, and other neurological diseases from Okayama University Hospital. Results A total of 29.6% of patients wanted to use telemedicine. Patients with headaches (60.0%) and epilepsy (38.1%) were more likely to want to use telemedicine than patients with PD (17.8%) or stroke (19.0%). Almost 90% of patients had access to a digital device, and there was no association between favoring telemedicine, ownership of a digital device, hospital visiting time, or waiting time at the hospital, although age was associated with motivation to telemedicine use (52.6 vs. 62.2 years old, p<0.001). Conclusion We can contribute to the management of the COVID-19 pandemic and the medical economy by promoting telemedicine, especially for young patients with headaches or epilepsy.