scholarly journals Lacunar stroke: mechanisms and therapeutic implications

2021 ◽  
pp. jnnp-2021-326308
Author(s):  
Shadi Yaghi ◽  
Eytan Raz ◽  
Dixon Yang ◽  
Shawna Cutting ◽  
Brian Mac Grory ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Treatment Strategies ◽  
Case Series ◽  
Underlying Mechanism ◽  
Neurological Deterioration ◽  
Lacunar Stroke ◽  
Therapeutic Implications ◽  
Novel Treatment Strategies ◽  
Neurovascular Imaging

Lacunar stroke is a marker of cerebral small vessel disease and accounts for up to 25% of ischaemic stroke. In this narrative review, we provide an overview of potential lacunar stroke mechanisms and discuss therapeutic implications based on the underlying mechanism. For this paper, we reviewed the literature from important studies (randomised trials, exploratory comparative studies and case series) on lacunar stroke patients with a focus on more recent studies highlighting mechanisms and stroke prevention strategies in patients with lacunar stroke. These studies suggest that lacunar stroke is a heterogeneous disease with various mechanisms, including most commonly lipohyalinosis and less commonly atheromatous disease and cardioembolism, highlighting the importance of a careful review of brain and neurovascular imaging, a cardiac and systemic evaluation. A better understanding of pathomechanisms of neurological deterioration may lead to investigating the utility of novel treatment strategies and optimisation of short-term antithrombotic treatment strategies to reduce the risk of neurological deterioration and prevent long-term disability in patients with lacunar stroke.

scholarly journals Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

Metabolites ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 72 ◽  
Author(s):  
Elke Humer ◽  
Thomas Probst ◽  
Christoph Pieh
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Treatment Strategies ◽  
Mood Stabilizers ◽  
Psychiatric Medication ◽  
Mitochondrial Regulation ◽  
Novel Treatment Strategies ◽  
Insight Into ◽  
Test Treatment

Biomarkers are a recent research target within biological factors of psychiatric disorders. There is growing evidence for deriving biomarkers within psychiatric disorders in serum or urine samples in humans, however, few studies have investigated this differentiation in brain or cerebral fluid samples in psychiatric disorders. As brain samples from humans are only available at autopsy, animal models are commonly applied to determine the pathogenesis of psychiatric diseases and to test treatment strategies. The aim of this review is to summarize studies on biomarkers in animal models for psychiatric disorders. For depression, anxiety and addiction disorders studies, biomarkers in animal brains are available. Furthermore, several studies have investigated psychiatric medication, e.g., antipsychotics, antidepressants, or mood stabilizers, in animals. The most notable changes in biomarkers in depressed animal models were related to the glutamate-γ-aminobutyric acid-glutamine-cycle. In anxiety models, alterations in amino acid and energy metabolism (i.e., mitochondrial regulation) were observed. Addicted animals showed several biomarkers according to the induced drugs. In summary, animal models provide some direct insights into the cellular metabolites that are produced during psychiatric processes. In addition, the influence on biomarkers due to short- or long-term medication is a noticeable finding. Further studies should combine representative animal models and human studies on cerebral fluid to improve insight into mental disorders and advance the development of novel treatment strategies.

scholarly journals Effects of cortisol administration on craving during in vivo exposure in patients with alcohol use disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leila M. Soravia ◽  
Franz Moggi ◽  
Dominique J.-F. de Quervain
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Underlying Mechanism ◽  
Double Blind ◽  
Extinction Memory ◽  
Exposure Sessions ◽  
Novel Treatment Strategies

AbstractAlcohol-associated memories and craving play a crucial role in the development and maintenance of alcohol use disorder (AUD). As treatment options are limited in AUD, novel treatment strategies focus on the manipulation of alcohol-associated memories. The stress hormone cortisol affects various memory processes, and first clinical studies have shown that it inhibits the retrieval of disorder-specific memories and enhances extinction memory. This study aimed to investigate the effects of a single oral administration of cortisol on craving in patients with AUD during repeated in vivo exposure to alcohol pictures and the preferred alcoholic drink. In a double-blind, block-randomized, placebo-controlled cross-over design, 46 patients with AUD were treated with two sessions of in vivo exposure to alcohol. Cortisol (20 mg) or placebo was orally administered 1 h before each test day. Craving, stress, and cortisol were repeatedly measured during exposure sessions. Results show, that cortisol administration had distinct effects on craving depending on the severity of AUD and test day. While cortisol administration significantly enhanced craving during exposure on the first test day in patients with less severe AUD, it reduced craving in patients with more severe AUD. Independent of the cortisol administration, repeated in vivo exposure reduced craving from test day 1 to test day 2. In conclusion, adding cortisol to in vivo exposure might be a promising approach for reducing the strength of alcohol-associated memories and might promote the consolidation of extinction memory in patients with severe AUD. However, the differential effect of cortisol on craving depending on AUD severity cannot be conclusively explained and highlights the need for future studies elucidating the underlying mechanism.

scholarly journals Mitophagy in Parkinson’s Disease: From Pathogenesis to Treatment

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 712 ◽  
Author(s):  
Jia Liu ◽  
Weijin Liu ◽  
Ruolin Li ◽  
Hui Yang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Strategies ◽  
Critical Component ◽  
Mitochondrial Quality Control ◽  
Therapeutic Implications ◽  
Novel Treatment ◽  
Mitochondrial Defects ◽  
Novel Treatment Strategies ◽  
Related Proteins

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD is complicated and remains obscure, but growing evidence suggests the involvement of mitochondrial and lysosomal dysfunction. Mitophagy, the process of removing damaged mitochondria, is compromised in PD patients and models, and was found to be associated with accelerated neurodegeneration. Several PD-related proteins are known to participate in the regulation of mitophagy, including PINK1 and Parkin. In addition, mutations in several PD-related genes are known to cause mitochondrial defects and neurotoxicity by disturbing mitophagy, indicating that mitophagy is a critical component of PD pathogenesis. Therefore, it is crucial to understand how these genes are involved in mitochondrial quality control or mitophagy regulation in the study of PD pathogenesis and the development of novel treatment strategies. In this review, we will discuss the critical roles of mitophagy in PD pathogenesis, highlighting the potential therapeutic implications of mitophagy regulation.

scholarly journals How I treat CNS lymphomas

Blood ◽  
2013 ◽  
Vol 122 (14) ◽  
pp. 2318-2330 ◽  
Author(s):  
James L. Rubenstein ◽  
Neel K. Gupta ◽  
Gabriel N. Mannis ◽  
Amanda K. LaMarre ◽  
Patrick Treseler
Keyword(s):  
Current Knowledge ◽  
Treatment Strategies ◽  
Cns Lymphoma ◽  
Clinical Neuropsychology ◽  
Term Survival ◽  
The Past ◽  
Dismal Prognosis ◽  
Novel Treatment Strategies ◽  
Cns Lymphomas

Abstract The pathogenesis of primary and secondary central nervous system (CNS) lymphoma poses a unique set of diagnostic, prognostic, and therapeutic challenges. During the past 10 years, there has been significant progress in the elucidation of the molecular properties of CNS lymphomas and their microenvironment, as well as evolution in the development of novel treatment strategies. Although a CNS lymphoma diagnosis was once assumed to be uniformly associated with a dismal prognosis, it is now reasonable to anticipate long-term survival, and possibly a cure, for a significant fraction of CNS lymphoma patients. The pathogenesis of CNS lymphomas affects multiple compartments within the neuroaxis, and proper treatment of the CNS lymphoma patient requires a multidisciplinary team with expertise not only in hematology/oncology but also in neurology, neuroradiology, neurosurgery, clinical neuropsychology, ophthalmology, pathology, and radiation oncology. Given the evolving principles of management and the evidence for improvements in survival, our goal is to provide an overview of current knowledge regarding the pathogenesis of CNS lymphomas and to highlight promising strategies that we believe to be most effective in establishing diagnosis, staging, and therapeutic management.

Abstract TP39: Long-term Imaging Outcomes in Cerebral Small Vessel Disease

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yan Chen ◽  
Renyuan Liu ◽  
Wu Xu ◽  
Yuanyuan Gao ◽  
Xin Xu ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Lacunar Stroke ◽  
Vessel Disease ◽  
Drum Tower Hospital ◽  
The Relationship

Background: About 90% Older people above the age of 65 years present white matter hyperintensities (WMH) of varying severity when undergoing MRI. However, white matter hyperintensities is one of the characteristic in imaging for cerebral small vessel disease (CSVD). The relationship between WMH volume and lacunar stroke is unknown. Patients and Methods: A total of 8475 patients with hypertension and WMH on MRI, which were from Nanjing Drum Tower hospital imaging register center from 2011 to 2015, were studied retrospectively. Age between 60 and 85 years without dementia or parkinsonism. The patients were scanned MRI including DWI, T1W, T2W, FLAIR in 1 time each year, acute lacunar stroke is as an endpoint. Patients with Intracranial atherosclerosis in larger arteries were excluded. Areas of supratentorial WMH were semi-automated segmented on FLAIR sequences using MRIcron software. DWI identificates acute lacunar infarct. Results: Of 8475 patients, 599 got acute lacunar stroke and accound for 7.07%. A percentage of 82.5 acute lacunar infarctions were located beside periventricular WMH and merge into white matter disease abnormalities. In compared with patients that were spared from any vascular incidents, higher periventricular WMH volumes were found among the 599 patients in baseline FLAIR images (p=0.012). Furthermore, by annual MRI scan, about 612 patients were found with increased volumes of periventricular WMH, and 86.5% of the patients ended up with acute lacunar stroke. While in patients with stable WMH volumes, only 0.89% of them ended up with vascular incidents. Logistic regression analysis demonstrated that only periventricular WMH volumes were associated with incidence of acute lacunar stroke (p=0.001), while no association of aging (p=0.275) and hypertension (p=0.146) were found. Conclusion: This study indicates that periventricular WMH volumes on FLAIR are independent predictors for acute lacunar stroke and suggest that therapies aimed at reducing progression of white matter hyperintensities via regulating hyperintensities and end-arteriole damage may protect against acute lacunar stroke in clinic.

scholarly journals Revisiting the Impact of Neurodegenerative Proteins in Epilepsy: Focus on Alpha-Synuclein, Beta-Amyloid, and Tau

Biology ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 122 ◽  
Author(s):  
Yam Nath Paudel ◽  
Efthalia Angelopoulou ◽  
Christina Piperi ◽  
Iekhsan Othman ◽  
Mohd. Farooq Shaikh
Keyword(s):  
Tau Protein ◽  
Treatment Strategies ◽  
Underlying Mechanism ◽  
Alpha Synuclein ◽  
New Agents ◽  
Disease Modifying Therapy ◽  
Promising Therapeutic Approach ◽  
Novel Treatment Strategies ◽  
The Impact ◽  
Insight Into

Lack of disease-modifying therapy against epileptogenesis reflects the complexity of the disease pathogenesis as well as the high demand to explore novel treatment strategies. In the pursuit of developing new therapeutic strategies against epileptogenesis, neurodegenerative proteins have recently gained increased attention. Owing to the fact that neurodegenerative disease and epileptogenesis possibly share a common underlying mechanism, targeting neurodegenerative proteins against epileptogenesis might represent a promising therapeutic approach. Herein, we review the association of neurodegenerative proteins, such as α-synuclein, amyloid-beta (Aβ), and tau protein, with epilepsy. Providing insight into the α-synuclein, Aβ and tau protein-mediated neurodegeneration mechanisms, and their implication in epileptogenesis will pave the way towards the development of new agents and treatment strategies.

scholarly journals Case Report: Repeated Series of Ketamine Infusions in Patients With Treatment-Resistant Depression: Presentation of Five Cases

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Gałuszko-Wȩgielnik ◽  
Adam Włodarczyk ◽  
Wiesław Jerzy Cubała ◽  
Alina Wilkowska ◽  
Natalia Górska ◽  
...  
Keyword(s):  
Treatment Effectiveness ◽  
Treatment Strategies ◽  
Case Series ◽  
Antidepressant Effect ◽  
Type I ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
New Treatment

Purpose: Approximately 30% of patients with major depressive disorder (MDD) are treatment resistant. There is an unquestionable need for new treatment strategies. Subanesthetic doses of intravenous (IV) ketamine have a rapid antidepressant effect in treatment-resistant depression (TRD). This paper describes the efficacy of repeated series of intravenous ketamine infusions as an add-on treatment in five TRD inpatients.Methods: Eligible patients aged 43–63 were given eight ketamine infusions as an add-on treatment for patients with MDD. The subjects have readministered the intervention due to worsening depressive symptoms.Results: Of the five inpatients given ketamine as a series of eight infusions, one underwent three, and four had two treatment series. Four patients achieved remission after first series and three after the second series of ketamine infusions. The adverse reactions were mild and transient with no sequelae.Limitations: Presented case series applies to short-term intervention with IV ketamine as an add-on therapy. The results cannot be generalized to the long-term maintenance treatment nor other ketamine formulations as well as different administration schedules and dosing.Conclusions: This case series showed efficacy and safety of the repeated series of IV ketamine treatment in TRD in MDD and bipolar disorder type I. The subsequent interventions were safe and observed adverse events were mild and transient. Interestingly, the IV ketamine treatment at successive administrations seems to alter the major depression severity of the next affective episode. There is a critical need for further research regarding IV ketamine treatment effectiveness and long-term safety in future studies.

Small Vessel Disease

2016 ◽  
Author(s):  
Ji Y. Chong ◽  
Michael P. Lerario
Keyword(s):  
Blood Pressure ◽  
Antiplatelet Therapy ◽  
Stroke Prevention ◽  
Small Vessel Disease ◽  
Secondary Stroke Prevention ◽  
Lacunar Stroke ◽  
Pressure Management ◽  
Vessel Disease ◽  
Blood Pressure Management

Lacunar strokes are strongly associated with hypertension. Long-term blood pressure management is important after lacunar stroke. Antiplatelet therapy should be instituted for secondary stroke prevention.

scholarly journals Novel drug delivery strategies and gene therapy regimen as a promising perspective for management of psoriasis

2021 ◽  
Vol 87 ◽  
pp. 333-340
Author(s):  
Sujata Pralhad Sawarkar ◽  
Vijay Yadav
Keyword(s):  
Gene Therapy ◽  
Drug Carrier ◽  
Topical Therapy ◽  
Treatment Strategies ◽  
Autoimmune Disorder ◽  
Underlying Mechanism ◽  
Therapy Regimen ◽  
Maximum Penetration ◽  
Novel Treatment Strategies ◽  
Novel Drug

Psoriasis is an autoimmune disorder; however, an exact underlying mechanism responsible for psoriasis is yet not known. A hypothesis put forward is an abnormal proliferation of keratinocytes due to faulty signals brought about by T-cells. Due to the lack of evidence of the exact cause, a variety of treatments have been used of which topical therapy is usually the first option in most patients. Topical therapy has several shortcomings and barriers of drug delivary which may be effectively overcome using novel drug carrier systems which exhibit maximum penetration, controlled release, reduced irritancy and, overall, a better efficacy. Thus, novel treatment strategies based on gene therapy such as antisensing nucleotide, silencing RNA complex, stem cell therapy and antibody-based therapy are being envisaged. This review article discusses the concepts and background of current novel delivery systems and gene therapy tools for effective management of psoriasis.

scholarly journals Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Brian R. Weil ◽  
Cevher Ozcan
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Treatment Strategies ◽  
Disease Process ◽  
Hibernating Myocardium ◽  
Atrial Remodeling ◽  
Therapeutic Implications ◽  
Atrial Myocyte ◽  
Novel Treatment Strategies

Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.

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