ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
AbstractThe SARS-CoV-2 virus gains entry to cells by binding to angiotensin-converting enzyme 2 (ACE2). Since circumventricular organs and parts of the hypothalamus lack a blood –brain barrier, and immunohistochemical studies demonstrate that ACE2 is highly expressed in circumventricular organs which are intimately connected to the hypothalamus, and the hypothalamus itself, these might be easy entry points for SARS-CoV-2 into the brain via the circulation. High ACE2 prote in expression is found in the subfornical organ, area postrema, and the paraventricular nucleus of the hypothalamus (PVH). The subfornical organ and PV...
Source: NeuroMolecular Medicine - April 22, 2022 Category: Neurology Source Type: research
HCAR1-Mediated l-Lactate Signaling Suppresses Microglial Phagocytosis
AbstractMicroglia, the primary brain-resident immune cells, protect the brain from various harmful pathogens, insulting and maintaining its homeostasis by phagocytosing extracellular particles. How microglia are metabolically regulated by their microenvironment remains largely elusive. Here, we investigated how extracellular lactate, which is abundant in the brain and dynamically changes in pathological states, affects microglial phagocytotic ability. We show thatl-lactate reduces microglia phagocytic capacity in a Hydroxycarboxylic Acid Receptor 1 but not Monocarboxylate transporter 1-dependent manner. Our findings point ...
Source: NeuroMolecular Medicine - April 11, 2022 Category: Neurology Source Type: research
Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
AbstractAs a prototypical proinflammatory cytokine, interleukin-1 (IL-1) exacerbates the early post-stroke inflammation, whereas its neutralization is protective. To further investigate the underlying cell-type-specific IL-1 effects, we subjected IL-1 ( α/β) knockout (Il1−/−) and wildtype (WT) littermate mice to permanent middle cerebral artery occlusion (pMCAO) and assessed immune cell infiltration and cytokine production in the ischemic hemisphere by flow cytometry 24 h and 72 h after stroke.Il1−/− mice showed smaller infarcts and reduced neutrophil infiltration into the ischemic brain. We identified γδ T ...
Source: NeuroMolecular Medicine - April 6, 2022 Category: Neurology Source Type: research
The Biological Activity of 3-O-Acetyl-11-keto- β-Boswellic Acid in Nervous System Diseases
AbstractFrankincense is a hard gelatinous resin exuded byBoswellia serrata. It contains a complex array of components, of which acetyl-11-keto-beta-boswellic acid (AKBA), a pentacyclic triterpenoid of the resin class, is the main active component. AKBA has a variety of physiological actions, including anti-infection, anti-tumor, and antioxidant effects. The use of AKBA for the treatment of mental diseases has been documented as early as ancient Greece. Recent studies have found that AKBA has anti-aging and other neurological effects, suggesting its potential for the treatment of neurological diseases. This review focuses o...
Source: NeuroMolecular Medicine - March 18, 2022 Category: Neurology Source Type: research
MOG-Specific T Cells Lead to Spontaneous EAE with Multilocular B Cell Infiltration in the GF-IL23 Model
AbstractAlthough IL-23 and downstream signal transduction play essential roles in neuroinflammation, the local impact of IL-23 in multiple sclerosis is still not fully understood. Our previous study revealed that the central nervous system (CNS)-restricted expression of IL-23 in a mouse model with astrocyte-specific expression of IL-23, called GF-IL23 mice, leads to spontaneous formation of infiltrates in the brain, especially in the cerebellum. To further investigate the impact of CNS-specific IL-23-expression on neuroinflammation, we studied the GF-IL23 model in mice expressing a myelin oligodendrocyte glycoprotein (MOG)...
Source: NeuroMolecular Medicine - March 3, 2022 Category: Neurology Source Type: research
Sex Differences in Glioblastoma Immunotherapy Response
AbstractGlioblastoma (GBM), the most common primary malignant brain tumor, remains difficult to treat and shares phenotypes, including an aberrant immune response, with other neurological disorders. Understanding the cellular and molecular mechanisms underlying this pathological immune response remains a priority, particularly as standard of care for advanced cancers evolves to include immunotherapies, which have yet to show strong clinical efficacy in GBM. Epidemiological evidence supports a sex difference in GBM, with increased prevalence in males, and recent studies identified differences between males and females rangi...
Source: NeuroMolecular Medicine - March 1, 2022 Category: Neurology Source Type: research
Using Radiation Therapy to Prime and Propagate an Anti-tumor Immune Response Against Brain Tumors
AbstractImmunotherapies have demonstrated efficacy and survival benefits in some patients suffering from brain tumors; however, most do not respond and new approaches to enhance anti-tumor immunotherapeutic responses in the brain are needed. Radiotherapy remains a commonly used cancer treatment modality and can augment immunotherapeutic responses through multiple mechanisms. Recent preclinical studies may provide insight on how to optimally combine radiation and immunotherapies to maximize treatment efficacy. Unique aspects of the brain tumor microenvironment may play a critical role in limiting the successful application ...
Source: NeuroMolecular Medicine - March 1, 2022 Category: Neurology Source Type: research
Contemporary RNA Therapeutics for Glioblastoma
AbstractGlioblastoma (GBM) is the most common primary brain tumor in adults and is universally lethal with a median survival of less than two years with standard therapy. RNA-based immunotherapies have significant potential to establish a durable treatment response for malignant brain tumors including GBM. RNA offers clear advantages over antigen-focused approaches but cannot often be directly administered due to biological instability. This review will focus on utilization of RNA dendritic cell vaccines and RNA nanoparticle therapies in the treatment of GBM. RNA-pulsed dendritic cell vaccines have been shown to be safe in...
Source: NeuroMolecular Medicine - March 1, 2022 Category: Neurology Source Type: research
Stem-Like Cell Populations, p53-Pathway Activation and Mechanisms of Recurrence in Sonic Hedgehog Medulloblastoma
Abstract
While most Sonic Hedgehog-associated medulloblastomas (SHH-MBs) respond to therapeutic intervention, radiation therapy often causes deleterious long-term neurocognitive defects, especially in infants and young children. To limit neurological comorbidities, the development of a reduction-of-therapy treatment or de-escalation approach was investigated. Although retrospective analysis of MBs indicated low-dose therapy was potentially effective, clinical de-escalation trials showed poor outcomes in infant SHH-MBs and was prematurely terminated. Recent studies suggest the existence of cancer-stem-cell (CSC)-like cel...
Source: NeuroMolecular Medicine - March 1, 2022 Category: Neurology Source Type: research
