Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer.

Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

High-Volume Hospital Had Lower Mortality of Severe Intracerebral Hemorrhage Patients.

Objective: Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH. Methods: We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death. Results: Among 9,086 ICH patients who admitted to hospital during 18-month period, 6,756 (74.4%) and 2,330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p < 0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p < 0.05). Conclusion: The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

Prospero Homeobox 1 and Doublecortin Correlate with Neural Damage after Ischemic Stroke.

Objective: Markers of neuroinflammation during ischemic stroke are well characterized, but additional markers of neural damage are lacking. The study identified associations of behavioral disorders after stroke with histologic neural damage and molecular biological change. Methods: 8-week-old, 25g male mice of the C57BL/6J strain were subjected to middle cerebral artery occlusion (MCAO) to induce ischemic stroke. The control group was a healthy wild type (WT), and the experimental group were designed as a low severity MCAO1 and a high severity MCAO2 based on post-stroke neurological scoring. All groups underwent behavioral tests, real-time polymerase chain reaction (rt-PCR), triphenyltetrazolium chloride (TTC) staining and hematoxylin and eosin (H&E) staining. One-way analysis of variance (ANOVA) was used to analyze statistical significance between groups. Results: In TTC staining, MCAO1 showed 29.02% and MCAO2 showed 38.94% infarct volume (p<0.0001). The pro-inflammatory cytokine interleukin (IL)-1ß was most highly expressed in MCAO2 (WT 0.44 vs MCAO1 2.69 vs MCAO2 5.02, p<0.0001). From the distance to target in the Barnes maze test, WT had a distance of 178 cm, MCAO1 had a distance of 276 cm, and MCAO2 had a distance of 1051 (p=0.0015). The latency to target was 13.3 seconds for WT, 27.9 seconds for MCAO1, and 87.9 seconds for MCAO2 (p=0.0007). Prospero homeobox 1 (Prox1) was most highly expressed in MCAO2 (p=0.0004). Doublecortin (Dcx) was most highly expressed in MCAO2 (p<0.0001). Conclusion: The study demonstrated that histological damage to neural cells and changes in brain mRNA expression were associated with behavioral impairment after ischemic stroke. Prox1 and Dcx may be biomarkers of neural damage associated with long-term cognitive decline, and increased expression at the mRNA level was consistent with neural damage and long-term cognitive dysfunction.

Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway.

BACKGROUND: Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect. METHODS: Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane. RESULTS: When the upper part of a mouse brain was irradiated using a laser (0.2 W cm- 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway. CONCLUSION: This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas.

First-Pass Recanalization with EmboTrap II in Acute Ischemic Stroke (FREE-AIS): A Multicenter Prospective Study.

OBJECTIVE: We aimed to evaluate the efficacy of EmboTrap II in terms of first-pass recanalization and to determine whether it could yield favorable outcomes. MATERIALS AND METHODS: In this multicenter, prospective study, we consecutively enrolled patients who underwent mechanical thrombectomy using EmboTrap II as a front-line device. The primary outcome was the first pass effect (FPE) rate defined by modified Thrombolysis In Cerebral Infarction (mTICI) grade 2c or 3 by the first pass of EmboTrap II. In addition, modified FPE (mFPE; mTICI grade 2b-3 by the first pass of EmboTrap II), successful recanalization (final mTICI grade 2b-3), and clinical outcomes were assessed. We also analyzed the effect of FPE on a modified Rankin Scale (mRS) score of 0-2 at 3 months. RESULTS: Two hundred-ten patients (mean age ± standard deviation, 73.3 ± 11.4 years; male, 55.7%) were included. Ninety-nine patients (47.1%) had FPE, and mFPE was achieved in 150 (71.4%) patients. Successful recanalization was achieved in 191 (91.0%) patients. Among them, 164 (85.9%) patients underwent successful recanalization by exclusively using EmboTrap II. The time from groin puncture to FPE was 25.0 minutes (interquartile range, 17.0-35.0 minutes). Procedure-related complications were observed in seven (3.3%) patients. Symptomatic intracranial hemorrhage developed in 14 (6.7%) patients. One hundred twenty-three (58.9% of 209 completely followed) patients had an mRS score of 0-2. Sixteen (7.7% of 209) patients died during the follow-up period. Patients who had successful recanalization with FPE were four times more likely to have an mRS score of 0-2 than those who had successful recanalization without FPE (adjusted odds ratio, 4.13; 95% confidence interval, 1.59-10.8; p = 0.004). CONCLUSION: Mechanical thrombectomy using the front-line EmboTrap II is effective and safe. In particular, FPE rates were high. Achieving FPE was important for an mRS score of 0-2, even in patients with successful recanalization.

Long-term outcomes of carotid artery stenting in patients with carotid artery stenosis: A single-center 14-year retrospective analysis.

OBJECTIVE: Carotid artery stenting (CAS) is currently widely used for the treatment of carotid artery stenosis. The objective of this study was to analyze the outcomes of CAS performed in a single institution. METHODS: We retrospectively analyzed 313 CAS cases from January 2007 to December 2020, including 206 (66%) symptomatic and 107 (34%) asymptomatic cases. Procedure-related morbidity and mortality were assessed. Rates of periprocedural (≤30 days after CAS) and postprocedural ipsilateral strokes (>30 days after CAS) were also assessed. Logistic regression analysis was used to identify risk factors for the periprocedural complication, in-stent restenosis (ISR), and ipsilateral stroke. RESULTS: The success rate of CAS was 98%. Among 313 cases, 1 patient died due to hyperperfusion-related intracerebral hemorrhage (ICH). The CAS-related mortality rate was 0.31%. The overall incidence of periprocedural complications is 5.1%. A risk factor for periprocedural complication was a symptomatic carotid artery stenosis (7.3% vs. 0.9%, p=0.016). Twenty cases of ISR occurred during 63.7±42.1 months of follow-up. The overall incidence of ISR was 10.2% (20/196). A risk factors for ISR were diabetes mellitus (17.6% vs. 5.7%, p=0.008) and patients who used Open-cell stents (19.6% vs. 6.9%, p=0.010). The overall incidence of ipsilateral stroke is 5.6%. A risk factors for ipsilateral stroke was ISR (95% CI, p=0.002). CONCLUSIONS: CAS is a safe and effective procedure for carotid artery stenosis. Although the incidence of complications is low, fatal complication such as hyperperfusion- related ICH can occur. To prevent hyperperfusion-related ICH, several methods such as strict blood pressure (BP) control, intentional less widening of stenotic segment should be used. To prevent ISR or stroke occurrence, special attention should be paid to patients who have ISR or ipsilateral stroke risk factors.

Heparin-mimicking polymer-based hydrogel matrix regulates macrophage polarization by controlling cell adhesion.

The physicochemical properties of biomaterials influence cell adhesion, shape, and polarization of macrophages. In this study, we aimed to evaluate the polarization of macrophages in terms of the regulation of cell adhesion and how synthetic mimics for heparin and poly(sodium-4-styrenesulfonate) can regulate macrophage polarization by modulating cell shape, focal adhesion, cell traction force, and intracellular tension. Our initial findings showed that macrophages cultured with heparin-mimicking polymer-based hydrogel matrix showed reduced expression of cell adhesion markers such as integrins, vinculin, RhoA, and ROCK1/2 and reduced cell shape, elongation, cell-matrix traction force, and intracellular tension. Furthermore, we observed a significant decrease in cell adhesion in cells cultured on the hydrogel, resulting in the promotion of M1 polarization. These findings offer insights into the important roles of cell-matrix interactions in macrophage polarization and offer a platform for heparin-mimicking polymer-based hydrogel matrices to induce M1 polarization by inducing cell adhesion without classical activators.

Safety and Efficacy of Flow Diverter Therapy for Unruptured Intracranial Aneurysm Compared to Traditional Endovascular Strategy : A Multi-Center, Randomized, Open-Label Trial.

OBJECTIVE: Endovascular treatment of large, wide-necked intracranial aneurysms by coil embolization is often complicated by low rates of complete occlusion and high rates of recurrence. A flow diverter device has been shown to be safe and effective for the treatment of not only large and giant unruptured aneurysms, but small and medium aneurysms. However, in Korea, its use has only recently been approved for aneurysms <10 mm. This study aims to compare the safety and efficacy of flow diversion and coil embolization for the treatment of unruptured aneurysms ≥7 mm. METHODS: The participants will include patients aged between 19 and 75 years to be treated for unruptured cerebral aneurysms ≥7 mm for the first time or for recurrent aneurysms after initial endovascular coil embolization. Participants assigned to a flow diversion cohort will be treated using any of the following devices : Pipeline Flex Embolization Device with Shield Technology (Medtronic, Minneapolis, MN, USA), Surpass Evolve (Stryker Neurovascular, Fremont, CA, USA), and FRED or FRED Jr. (MicroVention, Tustin, CA, USA). Participants assigned to a coil embolization cohort will undergo traditional endovascular coiling. The primary endpoint will be complete occlusion confirmed by cerebral angiography at 12 months after treatment. Secondary safety outcomes will evaluate periprocedural and post-procedural complications for up to 12 months. RESULTS: The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. CONCLUSION: This article describes the aim and design of a multi-center, randomized, open-label trial to compare the safety and efficacy of flow diversion versus traditional endovascular treatment for unruptured cerebral aneurysms ≥7 mm.

Multiple Cerebral Hemorrhages Caused by Paradoxical Reperfusion Injury After Cranioplasty.

Cranioplasty-related reperfusion injury has rarely been reported. Although there are several hypotheses, particularly regarding the mechanisms of the event, clear evidence is lacking. Here, we report the case of an 84-year-old man with traumatic intracranial hemorrhage and subdural hematoma who underwent decompressive craniectomy and hematoma evacuation in the right hemisphere. After 45 days, cranioplasty was performed using titanium. A preoperative perfusion study with 99m-Tc-HMPAO brain single-photon emission tomography revealed diffuse hypoperfusion in the left cerebral hemisphere with decreased vascular reserve. After cranioplasty, multiple cerebral hemorrhages were observed on immediate postoperative computed tomography. Cerebral hemorrhage eventually improved without surgery. Here, we report a case with findings revealed through perfusion studies before and after surgery.

Pharmacological Treatment for Neuroinflammation in Stress-Related Disorder.

Stress is an organism's response to a biological or psychological stressor, a method of responding to threats. The autonomic nervous system and hypothalamic-pituitary-adrenal axis (HPA axis) regulate adaptation to acute stress and secrete hormones and excitatory amino acids. This process can induce excessive inflammatory reactions to the central nervous system (CNS) by HPA axis, glutamate, renin-angiotensin system (RAS) etc., under persistent stress conditions, resulting in neuroinflammation. Therefore, in order to treat stress-related neuroinflammation, the improvement effects of several mechanisms of receptor antagonist and pharmacological anti-inflammation treatment were studied. The N-methyl-D-aspartate (NMDA) receptor antagonist, peroxisome proliferator-activated receptor agonist, angiotensin-converting enzyme inhibitor etc., effectively improved neuroinflammation. The interesting fact is that not only can direct anti-inflammation treatment improve neuroinflammation, but so can stress reduction or pharmacological antidepressants. The antidepressant treatments, including selective serotonin reuptake inhibitors (SSRI), also helped improve stress-related neuroinflammation. It presents the direction of future development of stress-related neuroinflammation drugs. Therefore, in this review, the mechanism of stress-related neuroinflammation and pharmacological treatment candidates for it were reviewed. In addition, treatment candidates that have not yet been verified but indicate possibilities were also reviewed.

Change of mortality of patients with acute ischemic stroke before and after 2015.

Introduction: Advances in the diagnosis and management of acute ischemic stroke (AIS) and the increased use of mechanical thrombectomy (MT) have improved the quality of care and prognosis of patients with AIS since 2015. We investigated the changing trends in mortality of patients with AIS in Korea before and after 2015. Materials and methods: A retrospective cohort study was conducted using combined anonymized data from the Acute Stroke Assessment Registry of Korea and the Health Insurance Review & Assessment Service database. Patients with ischemic stroke with precise onset time and initial National Institute of Health Stroke Scale records were included. Results: Patients receiving MT treatment increased from 256 (2.7%) pre-2015 to 1,037 (3.9%) post-2015 (p < 0.001). Overall mortality significantly decreased from pre-2015 to post-2015. In pre-2015, intravenous thrombolysis (IVT) administered within 2 h significantly reduced 3-month mortality when compared with non-IVT. While, in post-2015, IVT administered within 2 h significantly reduced the 3-month, 1-year, 2-year, and 4-year mortality (p < 0.05). MT only reduced 1-year mortality pre-2015; however, MT significantly reduced the 3-month, 1-year, and 2-year mortality post-2015 (p < 0.05). Post-stroke antiplatelet and anticoagulant drugs significantly reduced the 3-month, 1-year, 2-year, and 4-year mortality post-2015. Discussion: Since 2015, faster IVT has significantly reduced the short- and long-term mortality in patients with AIS; MT reduced the 3-month, 1-year, and 2-year mortality. Post-stroke antithrombotic medication has significantly lowered the 2- and 4-year mortality since 2015. Conclusions: Changing trends in AIS management since 2015 have improved the prognosis of patients with AIS.

Utility of Exosomes in Ischemic and Hemorrhagic Stroke Diagnosis and Treatment.

Stroke is the leading cause of death and neurological disorders worldwide. However, diagnostic techniques and treatments for stroke patients are still limited for certain types of stroke. Intensive research has been conducted so far to find suitable diagnostic techniques and treatments, but so far there has been no success. In recent years, various studies have drawn much attention to the clinical value of utilizing the mechanism of exosomes, low toxicity, biodegradability, and the ability to cross the blood-brain barrier. Recent studies have been reported on the use of biomarkers and protective and recovery effects of exosomes derived from stem cells or various cells in the diagnostic stage after stroke. This review focuses on publications describing changes in diagnostic biomarkers of exosomes following various strokes and processes for various potential applications as therapeutics.

Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect.

The low-density-lipoprotein receptor (LDLr) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood-brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (ApoE) regulates the levels of amyloid beta (Aß) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits.

Short- and long-term mortality of subarachnoid hemorrhage according to hospital volume and severity using a nationwide multicenter registry study.

Introduction: Recent improvements in treatment for subarachnoid hemorrhage (SAH) have decreased the mortality rates; however, the outcomes of SAH management are dependent on many other factors. In this study, we used nationwide, large-scale, observational data to investigate short- and long-term mortality rates after SAH treatment and the influence of patient severity and hospital volume. Patients and methods: We selected patients with SAH treated with clipping and coiling from the South Korean Acute Stroke Assessment Registry. High- and low-volume hospitals performed ≥20 clipping and coiling procedures and <20 clipping and coiling procedures per year, respectively. Short- and long-term mortality were tracked using data from the Health Insurance Review and Assessment Service. Results: Among 2,634 patients treated using clipping and coiling, 1,544 (58.6%) and 1,090 (41.4%) were hospitalized in high- and low-volume hospitals, respectively, and 910 (34.5%) and 1,724 (65.5%) were treated with clipping and coiling, respectively. Mortality rates were 13.5, 14.4, 15.2, and 16.1% at 3 months, 1, 2, and 4 years, respectively. High-volume hospitals had a significantly lower 3-month mortality rate. Patients with mild clinical status had a significantly lower 3-month mortality rate in high-volume hospitals than in low-volume hospitals. Patients with severe clinical status had significantly lower 1- and 2-year mortality rates in high-volume hospitals than in low-volume hospitals. Conclusion: Short- and long-term mortality in patients with SAH differed according to hospital volume. In the modern endovascular era, clipping and coiling can lead to better outcomes in facilities with high stroke-care capabilities.

ROCK and PDE-5 Inhibitors for the Treatment of Dementia: Literature Review and Meta-Analysis.

Dementia is a disease in which memory, thought, and behavior-related disorders progress gradually due to brain damage caused by injury or disease. It is mainly caused by Alzheimer's disease or vascular dementia and several other risk factors, including genetic factors. It is difficult to treat as its incidence continues to increase worldwide. Many studies have been performed concerning the treatment of this condition. Rho-associated kinase (ROCK) and phosphodiesterase-5 (PDE-5) are attracting attention as pharmacological treatments to improve the symptoms. This review discusses how ROCK and PDE-5 affect Alzheimer's disease, vascular restructuring, and exacerbation of neuroinflammation, and how their inhibition helps improve cognitive function. In addition, the results of the animal behavior analysis experiments utilizing the Morris water maze were compared through meta-analysis to analyze the effects of ROCK inhibitors and PDE-5 inhibitors on cognitive function. According to the selection criteria, 997 publications on ROCK and 1772 publications on PDE-5 were screened, and conclusions were drawn through meta-analysis. Both inhibitors showed good improvement in cognitive function tests, and what is expected of the synergy effect of the two drugs was confirmed in this review.

Optimal Duration of Dual Antiplatelet Therapy after Stent- Assisted Coil Embolization of Unruptured Intracranial Aneurysms : A Prospective Randomized Multicenter Trial.

OBJECTIVE: Stent-assisted coil embolization (SAC) has been increasingly used to treat various types of intracranial aneurysms. Delayed thromboembolic complications are major concerns regarding this procedure, so dual antiplatelet therapy with aspirin and clopidogrel is needed. However, clinicians vary the duration of dual antiplatelet therapy after SAC, and no randomized study has been performed. This study aims to compare the safety and efficacy of long-term (12 months) dual antiplatelet therapy and shortterm dual antiplatelet therapy (6 months) after SAC for patients with unruptured intracranial aneurysms (UIAs). METHODS: This is a prospective, randomized and multicenter trial to investigate the optimal duration of dual antiplatelet therapy after SAC in patients with UIAs. Subjects will receive dual antiplatelet therapy for 6 months (short-term group) or 12 months (longterm group) after SAC. The primary endpoint is the assessment of thromboembolic complications between 1 and 18 months after SAC. We will enroll 528 subjects (264 subjects in each group) and perform 1 : 1 randomization. This study will involve 14 topperforming, high-volume Korean institutions specializing in coil embolization. RESULTS: The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. CONCLUSION: This article describes that the aim of this prospective randomized multicenter trial is to compare the effect of short-term (6 months) and long-term (12 months) dual antiplatelet therapy on UIAs in patients undergoing SAC, and to find the optimal duration.

Neuroinflammation in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a well-known mental illness, which is caused by various stressors, including memories of past physical assaults and psychological pressure. It is diagnosed as a mental and behavioral disorder, but increasing evidence is linking it to the immune system and inflammatory response. Studies on the relationship between inflammation and PTSD revealed that patients with PTSD had increased levels of inflammatory cytokine biomarkers, such as interleukin-1, interleukin-6, tumor necrosis factor-α, nuclear factor-κB, and C-reactive protein, compared with healthy controls. In addition, animal model experiments imitating PTSD patients suggested the role of inflammation in the pathogenesis and pathophysiology of PTSD. In this review, we summarize the definition of PTSD and its association with increased inflammation, its mechanisms, and future predictable diseases and treatment possibilities. We also discuss anti-inflammatory treatments to address inflammation in PTSD.

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats.

OBJECTIVE: Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. METHODS: We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. RESULTS: Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. CONCLUSION: PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia.

Patients with vascular dementia, caused by cerebral ischemia, experience long-term cognitive impairment due to the lack of effective treatment. The mechanisms of and treatments for vascular dementia have been investigated in various animal models; however, the insufficient information on gene expression changes that define pathological conditions hampers progress. To investigate the underlying mechanism of and facilitate treatment development for vascular dementia, we established a mouse model of chronic cerebral hypoperfusion, including bilateral carotid artery stenosis, by using microcoils, and elucidated the molecular pathway underlying vascular dementia development. Rho-associated protein kinase (ROCK) 1/2, which regulates cellular structure, and inflammatory cytokines (IL-1 and IL-6) were upregulated in the vascular dementia model. However, expression of claudin-5, which maintains the blood-brain barrier, and MAP2 as a nerve cell-specific factor, was decreased in the hippocampal region of the vascular dementia model. Thus, we revealed that ROCK pathway activation loosens the tight junction of the blood-brain barrier and increases the influx of inflammatory cytokines into the hippocampal region, leading to neuronal death and causing cognitive and emotional dysfunction. Our vascular dementia model allows effective study of the vascular dementia mechanism. Moreover, the ROCK pathway may be a target for vascular dementia treatment development in the future.