scholarly journals The Nasal Route as a Potential Pathway for Delivery of Erythropoietin in the Treatment of Acute Ischemic Stroke in Humans

2009 ◽  
Vol 9 ◽  
pp. 970-981 ◽  
Author(s):  
Julio Cesar García-Rodríguez ◽  
Iliana Sosa Teste
Keyword(s):  
Neurodegenerative Disorders ◽  
Clinical Evidence ◽  
Nasal Administration ◽  
Intranasal Delivery ◽  
Neuroprotective Effects ◽  
Sialic Acid Content ◽  
Chemically Modified ◽  
Different Types ◽  
The Central Nervous System ◽  
The Brain

Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB) in order to deliver therapeutic agents to the brain. This method allows drugs that do not cross the BBB to be delivered to the central nervous system in a few minutes. With this technology, it will be possible to eliminate systemic administration and its potential side effects. Using the intranasal delivery system, researchers have demonstrated neuroprotective effects in different animal models of stroke using erythropoietin (EPO) as a neuroprotector or other different types of EPO without erythropoiesis-stimulating activity. These new molecules retain their ability to protect neural tissue against injury and they include Asialoerythropoietin (asialoEPO) carbamylated EPO (CEPO), and rHu-EPO with low sialic acid content (Neuro-EPO). Contrary to the other EPO variants, Neuro-EPO is not chemically modified, making it biologically similar to endogenous EPO, with the advantage of less adverse reactions when this molecule is applied chronically. This constitutes a potential benefit of Neuro-EPO over other variants of EPO for the chronic treatment of neurodegenerative illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic approach. However, it will be necessary to initiate clinical trials in stroke patients using intranasal delivery in order to obtain the clinical evidence of its neuroprotectant capacity in the treatment of patients with acute stroke and other neurodegenerative disorders. This new therapeutic approach could revolutionize the treatment of neurodegenerative disorders in the 21stcentury.

scholarly journals A Human 3D neural assembloid model for SARS-CoV-2 infection

2021 ◽  
Author(s):  
Lu Wang ◽  
David Sievert ◽  
Alex E. Clark ◽  
Hannah Federman ◽  
Benjamin D. Gastfriend ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Type I Interferon ◽  
Type I ◽  
Transcriptional Responses ◽  
The Central Nervous System ◽  
Membrane Components ◽  
Virus Spreading ◽  
The Brain ◽  
Basement Membrane Components

AbstractClinical evidence suggests the central nervous system (CNS) is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although mechanisms remain unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points1. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Prior to infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral ‘replication hubs’, with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new ‘assembloid’ model2 that supports SARS-CoV-2 entry and replication in neural tissue, and PCCOs serve as an experimental model for neural infection.

scholarly journals Daily Low Dose of Erythropoietin and Neuroinflammation

2020 ◽  
Author(s):  
Reza Nejat ◽  
Ahmad Shahir Sadr ◽  
Alireza Ebrahimi ◽  
Alireza Nabati ◽  
Elham Eshaghi
Keyword(s):  
Low Dose ◽  
High Dose ◽  
Neuroprotective Effects ◽  
Inflammatory Reactions ◽  
Daily Dose ◽  
Secondary Messengers ◽  
Probable Outcome ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Neuroinflammation, defined as inflammatory reactions mediated by cytokines, chemokines, reactive oxygen species, and secondary messengers in the central nervous system (CNS) including the brain and spinal cord is the basis of many neurological disorders [1] Recently, erythropoietin (EPO) has been considered and studied as a modulator of neuroinflammation.[2-4] On this article minireview of pathophysiology of neuroinflammation and the neuroprotective effects of EPO is discussed and a case of subacute huge subdural hematoma with double mydriasis operated urgently, treated with low daily dose (vs high dose once or twice a month in the literature) of EPO and recovered fully and discharged home with good consciousness is reported. In addition, the probable outcome of erythropoietin administration in patients with neuroinflammation in COVID19 is considered.

scholarly journals Modulation of Glial Function in Health, Aging, and Neurodegenerative Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Kendra L. Hanslik ◽  
Kaitlyn M. Marino ◽  
Tyler K. Ulland
Keyword(s):  
Synaptic Plasticity ◽  
Immune Cells ◽  
Neurodegenerative Disorders ◽  
Ion Homeostasis ◽  
Neuronal Dysfunction ◽  
Health Aging ◽  
Glial Function ◽  
The Central Nervous System ◽  
The Brain

In the central nervous system (CNS), glial cells, such as microglia and astrocytes, are normally associated with support roles including contributions to energy metabolism, synaptic plasticity, and ion homeostasis. In addition to providing support for neurons, microglia and astrocytes function as the resident immune cells in the brain. The glial function is impacted by multiple aspects including aging and local CNS changes caused by neurodegeneration. During aging, microglia and astrocytes display alterations in their homeostatic functions. For example, aged microglia and astrocytes exhibit impairments in the lysosome and mitochondrial function as well as in their regulation of synaptic plasticity. Recent evidence suggests that glia can also alter the pathology associated with many neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Shifts in the microbiome can impact glial function as well. Disruptions in the microbiome can lead to aberrant microglial and astrocytic reactivity, which can contribute to an exacerbation of disease and neuronal dysfunction. In this review, we will discuss the normal physiological functions of microglia and astrocytes, summarize novel findings highlighting the role of glia in aging and neurodegenerative diseases, and examine the contribution of microglia and astrocytes to disease progression.

scholarly journals Daily Low Dose of Erythropoietin in Neuroinflammation; EPO Might Be Hazardous in COVID-19

2020 ◽  
Author(s):  
Reza Nejat ◽  
Ahmad Shahir Sadr ◽  
Alireza Ebrahimi ◽  
Alireza Nabati ◽  
Elham Eshaghi
Keyword(s):  
Neurological Disorders ◽  
Low Dose ◽  
High Dose ◽  
Neuroprotective Effects ◽  
Inflammatory Reactions ◽  
Daily Dose ◽  
Secondary Messengers ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Neuroinflammation, defined as inflammatory reactions mediated by cytokines, chemokines, reactive oxygen species, and secondary messengers in the central nervous system (CNS) including the brain and spinal cord is the basis of many neurological disorders. Recently, erythropoietin (EPO) has been considered and studied as a modulator of neuroinflammation. On this article minireview of pathophysiology of neuroinflammation and the neuroprotective effects of EPO is discussed and a case of subacute huge subdural hematoma with double mydriasis operated urgently, treated with low daily dose (vs high dose once or twice a month in the literature) of EPO and recovered fully and discharged home with good consciousness is reported. In addition, the probable unfavorable outcome of erythropoietin administration in patients with neuroinflammation in COVID-19 is considered.

Actinomycosis of the brain

1985 ◽  
Vol 63 (1) ◽  
pp. 131-133 ◽  
Author(s):  
He Chen-wei
Keyword(s):  
Central Nervous System ◽  
Rare Case ◽  
Surgical Excision ◽  
Content Type ◽  
Different Types ◽  
Excellent Health ◽  
The Central Nervous System ◽  
The Brain ◽  
Fine Print

✓ A rare case of actinomycosis of the brain is reported. The patient recovered after surgical excision of the lesion and a prolonged course of antibiotic therapy. At follow-up examination 25 months later, the patient was in excellent health. Different types of actinomycotic infections of the central nervous system are reviewed and the diagnosis and treatment of this disease are discussed.

scholarly journals Parkinson’s Disease and Autophagy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ana María Sánchez-Pérez ◽  
Berta Claramonte-Clausell ◽  
Juan Vicente Sánchez-Andrés ◽  
María Trinidad Herrero
Keyword(s):  
Cell Death ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Causal Relationship ◽  
Neurodegenerative Disorders ◽  
Therapeutic Strategy ◽  
Neuroprotective Effects ◽  
Autophagy Induction ◽  
Effective Therapeutic Strategy ◽  
The Brain

It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy.

scholarly journals A Human 3D neural assembloid model for SARS-CoV-2 infection

2021 ◽  
Author(s):  
Joseph Gleeson ◽  
Lu Wang ◽  
David Sievert ◽  
Alex Clark ◽  
Hannah Federman ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Type I Interferon ◽  
Type I ◽  
Transcriptional Responses ◽  
The Central Nervous System ◽  
Membrane Components ◽  
Virus Spreading ◽  
The Brain ◽  
Basement Membrane Components

Abstract Clinical evidence suggests the central nervous system (CNS) is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although mechanisms remain unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points1. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Prior to infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral ‘replication hubs’, with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new ‘assembloid’ model2 that supports SARS-CoV-2 entry and replication in neural tissue, and PCCOs serve as an experimental model for neural infection.

scholarly journals Ingredients for Functional Drinks in Neurodegenerative Diseases: A Review

2009 ◽  
Vol 4 (5) ◽  
pp. 1934578X0900400
Author(s):  
Pilar Zafrilla ◽  
Juana M Morulas ◽  
José M. Rubio-Perez ◽  
Emma Cantos Villar
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Clinical Evidence ◽  
The Body ◽  
Neuroprotective Effects ◽  
Antioxidant Agents ◽  
Rate Of Progression ◽  
The Brain

Several studies have indicated that oxidative stress is a major risk factor for the initiation and progression of neurological disorders like Parkinson's disease (PD) and Alzheimer's (AD). Therefore, reducing oxidative stress appears to be a rational choice for the prevention and reduction in the rate of progression of these neurological disorders. The brain utilizes about 25% of respired oxygen even though it represents only 5% of the body weight. Free radicals are generated during the normal intake of oxygen, during infection, and during normal oxidative metabolism of certain substrates. Although experimental data are consistent in demonstrating the neuroprotective effects of antioxidants in vitro and in animal models, the clinical evidence that antioxidant agents may prevent or slow the course of these diseases is still relatively unsatisfactory, and insufficient to strongly modify clinical practice. In this paper, natural possible substances that could be added to a beverage to prevent or decrease the developing of neurodegenerative diseases are reviewed.

Efficient brain targeting and therapeutic intracranial activity of bortezomib through intranasal co-delivery with NEO100 in rodent glioblastoma models

2020 ◽  
Vol 132 (3) ◽  
pp. 959-967 ◽  
Author(s):  
Weijun Wang ◽  
Steve Swenson ◽  
Hee-Yeon Cho ◽  
Florence M. Hofman ◽  
Axel H. Schönthal ◽  
...  
Keyword(s):  
Brain Lesion ◽  
Systemic Exposure ◽  
Brain Targeting ◽  
Brain Delivery ◽  
Intranasal Delivery ◽  
Systemic Delivery ◽  
Pharmaceutical Agent ◽  
The Central Nervous System ◽  
Pharmaceutical Agents ◽  
The Brain

OBJECTIVEMany pharmaceutical agents are highly potent but are unable to exert therapeutic activity against disorders of the central nervous system (CNS), because the blood-brain barrier (BBB) impedes their brain entry. One such agent is bortezomib (BZM), a proteasome inhibitor that is approved for the treatment of multiple myeloma. Preclinical studies established that BZM can be effective against glioblastoma (GBM), but only when the drug is delivered via catheter directly into the brain lesion, not after intravenous systemic delivery. The authors therefore explored alternative options of BZM delivery to the brain that would avoid invasive procedures and minimize systemic exposure.METHODSUsing mouse and rat GBM models, the authors applied intranasal drug delivery, where they co-administered BZM together with NEO100, a highly purified, GMP-manufactured version of perillyl alcohol that is used in clinical trials for intranasal therapy of GBM patients.RESULTSThe authors found that intranasal delivery of BZM combined with NEO100 significantly prolonged survival of tumor-bearing animals over those that received vehicle alone and also over those that received BZM alone or NEO100 alone. Moreover, BZM concentrations in the brain were higher after intranasal co-delivery with NEO100 as compared to delivery in the absence of NEO100.CONCLUSIONSThis study demonstrates that intranasal delivery with a NEO100-based formulation enables noninvasive, therapeutically effective brain delivery of a pharmaceutical agent that otherwise does not efficiently cross the BBB.

scholarly journals Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?

2019 ◽  
Vol 20 (16) ◽  
pp. 3858 ◽  
Author(s):  
Kevin Mouzat ◽  
Aleksandra Chudinova ◽  
Anne Polge ◽  
Jovana Kantar ◽  
William Camu ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Target Genes ◽  
Major Constituent ◽  
Liver X Receptors ◽  
Neuroprotective Effects ◽  
Brain Cholesterol ◽  
Pharmacological Targets ◽  
The Central Nervous System ◽  
X Receptors ◽  
Lateral Sclerosis

Liver X Receptors (LXR) alpha and beta are two members of nuclear receptor superfamily documented as endogenous cholesterol sensors. Following conversion of cholesterol in oxysterol, both LXR isoforms detect intracellular concentrations and act as transcription factors to promote expression of target genes. Among their numerous physiological roles, they act as central cholesterol-lowering factors. In the central nervous system (CNS), cholesterol has been shown to be an essential determinant of brain function, particularly as a major constituent of myelin and membranes. In the brain, LXRs act as cholesterol central regulators, and, beyond this metabolic function, LXRs have additional roles such as providing neuroprotective effects and lowering neuroinflammation. In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and multiple sclerosis (MS), dysregulations of cholesterol and oxysterol have been reported. In this paper, we propose to focus on recent advances in the knowledge of the LXRs roles on brain cholesterol and oxysterol homeostasis, neuroinflammation, neuroprotection, and their putative involvement in neurodegenerative disorders. We will discuss their potential use as candidates for both molecular diagnosis and as promising pharmacological targets in the treatment of ALS, AD, or MS patients.

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