Emergence of the brain-border immune niches and their contribution to the development of neurodegenerative diseases.

Historically, the central nervous system (CNS) was regarded as 'immune-privileged', possessing its own distinct immune cell population. This immune privilege was thought to be established by a tight blood-brain barrier (BBB) and blood-cerebrospinal-fluid barrier (BCSFB), which prevented the crossing of peripheral immune cells and their secreted factors into the CNS parenchyma. However, recent studies have revealed the presence of peripheral immune cells in proximity to various brain-border niches such as the choroid plexus, cranial bone marrow (CBM), meninges, and perivascular spaces.

Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.

Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain.

Optimal Therapeutic Strategy of Bone Marrow-Originated Autologous Mesenchymal Stromal/Stem Cells for ALS.

Amyotrophic lateral sclerosis (ALS) is characterized by selective and progressive neurodegenerative changes in motor neural networks. Given the system complexity, including anatomically distributed sites of degeneration from the motor cortex to the spinal cord and chronic pro-inflammatory conditions, a cell-based therapeutic strategy could be an alternative approach to treating ALS. Lessons from previous mesenchymal stromal/stem cell (MSC) trials in ALS realized the importance of 3 aspects in current and future MSC therapy, including the preparation of MSCs, administration routes and methods, and recipient-related factors.

Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression.

Postpartum depression (PPD) is another type of depression, including emotional fluctuation, fatigue, and anxiety. Based on the specific event like giving birth, it can be speculated that PPD might have its specific mechanism. Here, we confirmed that dexamethasone (DEX) administration during pregnancy (gestational days 16-18) induced depressive- and anxiety-like behaviors in dam (DEX-dam) after weaning period (3 weeks).

Role of NCKAP1 in the Defective Phagocytic Function of Microglia-Like Cells Derived from Rapidly Progressing Sporadic ALS.

Microglia plays a key role in determining the progression of amyotrophic lateral sclerosis (ALS), yet their precise role in ALS has not been identified in humans. This study aimed to identify a key factor related to the functional characteristics of microglia in rapidly progressing sporadic ALS patients using the induced microglia model, although it is not identical to brain resident microglia. After confirming that microglia-like cells (iMGs) induced by human monocytes could recapitulate the main signatures of brain microglia, step-by-step comparative studies were conducted to delineate functional differences using iMGs from patients with slowly progressive ALS [ALS(S), n = 14] versus rapidly progressive ALS [ALS(R), n = 15].

A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder.

Few studies report the microglia involvement in the pathogenesis of panic disorder (PD), although the crucial role of microglia in other neuropsychiatric diseases is being emphasized. In addition, there is no report to characterize the phenotypic and functional levels of PD patient-derived microglia to find their clinical relevance. Herein, we used a model to induce patient-derived microglia-like cells (iMGs) to clarify the molecular characteristics and function of PD-iMGs.

Advanced therapeutic strategies targeting microglia: beyond neuroinflammation.

For a long time, microglia have been recognized as the main culprits of neuroinflammatory responses because they are primary phagocytes present in the parenchyma of the central nervous system (CNS). However, with the evolving concept of microglial biology, advanced and precise approaches, rather than the global inhibition of activated microglia, have been proposed in the management of neurological disorders. Yolk sac-derived resident microglia have heterogeneous composition according to brain region, sex, and diseases.

A Step-by-step Protocol for Obtaining Mature Microglia from Mice.

In mice, microglial precursors in the yolk sac migrate to the brain parenchyma through the head neuroepithelial layer between embryonic days 8.5 (E8.5)-E16.

Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure.

Fetal microglia that are particularly sensitive cells to the changes in utero environment might be involved in the sex-biased onset and vulnerability to psychiatric disorders. To address this issue, we administered a 50 µg/kg dexamethasone (DEX) to dams subcutaneously from gestational days 16 to 18 and a series of behavioral assessments were performed in the offspring. Prenatal exposure to dexamethasone (PN-DEX) induced schizophrenia (SCZ)-relevant behaviors in male mice and depressive-like behavior in female mice.

Fluoxetine Decreases Phagocytic Function via REV-ERBα in Microglia.

Although fluoxetine (FLX) is a commonly used drug in psychiatric disorders, such as major depressive disorder, anxiety disorder, panic disorder, and obsessive-compulsive disorder, the mechanism by which FLX exerts its therapeutic effect is not completely understood. In this study, we aimed to determine the possible mechanism by which FLX focuses on microglial phagocytosis. FLX reduced phagocytic function in BV2 cells and increased REV-ERBα without affecting other microglia-related genes, such as inflammation and phagocytosis.

Persistent Acidic Environment Induces Impaired Phagocytosis via ERK in Microglia.

Acidic environment evoked by stroke, traumatic brain injury, and Alzheimer's disease may change the functional properties of microglia. Nevertheless, the underlying mechanisms of functional changes in microglia remain unclear. In this study, we found that acidic stimuli (pH 6.

Aged Microglia in Neurodegenerative Diseases: Microglia Lifespan and Culture Methods.

Microglia have been recognized as macrophages of the central nervous system (CNS) that are regarded as a culprit of neuroinflammation in neurodegenerative diseases. Thus, microglia have been considered as a cell that should be suppressed for maintaining a homeostatic CNS environment. However, microglia ontogeny, fate, heterogeneity, and their function in health and disease have been defined better with advances in single-cell and imaging technologies, and how to maintain homeostatic microglial function has become an emerging issue for targeting neurodegenerative diseases.

Possible role of arginase 1 positive microglia on depressive/anxiety-like behaviors in atopic dermatitis mouse model.

Atopic dermatitis (AD) and mood disorder comorbidities are typical, but the exact mechanism underlying their interplay has not been clarified. In this study, we aimed to identify the possible mechanisms of anxiety/depressive-like behaviors observed in AD, focusing on microglia. AD was induced by Dermatophagoides farinae body extract (Dfb) in NC/Nga mice and anxiety/depressive-like behaviors were analyzed by behavioral assessments such as open field test (OFT), tail suspension test (TST), sucrose preference test (SPT), and social interaction.

A new method for obtaining bankable and expandable adult-like microglia in mice.

Background: The emerging role of microglia in neurological disorders requires a novel method for obtaining massive amounts of adult microglia. We aim to develop a new method for obtaining bankable and expandable adult-like microglia in mice.

Methods: The head neuroepithelial layer (NEL) that composed of microglial progenitor and neuroepithelial cells at mouse E13.

White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder.

Objective: Regarding the neuroinflammatory theory of major depressive disorder (MDD), little is known about the effect of pro-inflammatory cytokines on white matter (WM) changes in MDD. We aimed to investigate the relationship between pro-inflammatory cytokines and WM alterations in patients with MDD.

Methods: Twenty-two patients with MDD and 22 healthy controls (HC) were evaluated for brain imaging and pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, interferon-γ and tumor necrosis factor (TNF)-α.

Chronically infused angiotensin II induces depressive-like behavior via microglia activation.

Brain inflammation is one of hypotheses explaining complex pathomechanisms of depression. Angiotensin II (ANGII), which is associated with hypertension, also induces brain inflammation. However, there is no animal study showing the direct relationship between ANGII and depression.

Human umbilical cord-derived mesenchymal stem cells alleviate schizophrenia-relevant behaviors in amphetamine-sensitized mice by inhibiting neuroinflammation.

At present, therapeutic options available for treating schizophrenia are limited to monoamine-based antipsychotic drugs. Recent genome wide association study (GWAS) indicated a close relationship between immune system and schizophrenia. To leverage the GWAS finding for therapeutic strategy, we conducted a mechanism and effect study on application of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with potent immune-modulatory effect in an animal model useful for the study of schizophrenia.

Closure of oroantral fistula: a review of local flap techniques.

Oroantral fistula (OAF), also termed oroantral communication, is an abnormal condition in which there is a communicating tract between the maxillary sinus and the oral cavity. The most common causes of this pathological communication are known to be dental implant surgery and extraction of posterior maxillary teeth. The purpose of this article is to describe OAF; introduce the approach algorithm for the treatment of OAF; and review the fundamental surgical techniques for fistula closure with their advantages and disadvantages.

Development of Collagen-Based 3D Matrix for Gastrointestinal Tract-Derived Organoid Culture.

Organoid is a cell organization grown in a three-dimensional (3D) culture system which represents all characteristics of its origin. However, this organ-like structure requires supporting matrix to maintain its characteristics and functions. Matrigel, derived from mouse sarcoma, has often been used as the supporting matrix for organoids, but the result may not be desirable for clinical applications because of the unidentified components from the mouse sarcoma.

evaluation of scaffolds compatible for colonoid engraftments onto injured mouse colon epithelium.

Colon organoids (colonoids) are known to be similar to colon tissue in structure and function, which makes them useful in the treatment of intestinal de-epithelialized disease. Matrigel, which is used as a transplantation scaffold for colonoids, cannot be used in clinical applications because of its undefined composition and tumorigenicity. This study identifies clinically available scaffolds that are effective for colonoid transplantation in damaged intestinal mucosa.

The International Knee Documentation Committee Score Indicates Midterm Patient Satisfaction with Outcomes after Meniscal Allograft Transplantation.

Background: This study aimed to identify the factors associated with patient satisfaction with the outcome of meniscal allograft transplantation (MAT).

Materials And Methods: Patients treated with MAT from March 2006 to May 2009 were asked to complete a five-point Likert scale regarding satisfaction with the outcome of MAT, in addition to the following subjective outcome evaluation forms: the International Knee Documentation Committee (IKDC) subjective forms, Knee Society Score knee and function forms, and Lysholm Knee Scoring Scale. We collected radiologic data using X-ray and magnetic resonance imaging and assessed isokinetic muscle strength test using the Biodex System 3.

Differential effect of LPS and paclitaxel on microglial functional phenotypes and circulating cytokines: the possible role of CX3CR1 and IL-4/10 in blocking persistent inflammation.

Neuroinflammation plays a role in cancer chemotherapy-induced chronic pain. Thus far, most studies have focused on neuroinflammation suppression. However, there are limited reports of which factor is involved in the transition from acute inflammation to chronic inflammation, resulting in neuroinflammation and chronic pain.

Three-Dimensional computed tomography tunnel assessment of allograft anatomic reconstruction in chronic ankle instability: 33 cases.

Introduction: Although clinical results of anatomic reconstruction using allograft are reportedly good, studies on how accurately the tunnel has been made after surgery are very rare. The purpose of this study was to analyze the postoperative locations of the tunnels through 3-dimensional computed tomography (3D-CT) after anatomic ligament reconstruction and to evaluate its clinical results.

Hypothesis: We hypothesized that anatomic lateral ligament reconstruction could lead to excellent results in clinical outcomes by repositioning anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) accurately.

Repeated Intrathecal Mesenchymal Stem Cells for Amyotrophic Lateral Sclerosis.

Objective: To assess the safety and efficacy of 2 repeated intrathecal injections of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in amyotrophic lateral sclerosis (ALS).

Methods: In a phase 2 randomized controlled trial (NCT01363401), 64 participants with ALS were randomly assigned treatments (1:1) of riluzole alone (control group, n = 31) or combined with 2 BM-MSC injections (MSC group, n = 33). Safety was assessed based on the occurrence of adverse events.