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.

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.

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.

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.

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.

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.

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.