scholarly journals The role of brain gaseous neurotransmitters in anxiety

2021 ◽  
Vol 73 (2) ◽  
pp. 357-371
Author(s):  
Artur Pałasz ◽  
Itiana Castro Menezes ◽  
John J. Worthington
Keyword(s):  
Chemical Structure ◽  
Anxiolytic Effect ◽  
Treatment Schedule ◽  
Gas Release ◽  
Therapeutic Application ◽  
No Donors ◽  
Animal Models Of Anxiety ◽  
No Signaling ◽  
The Brain

AbstractAlthough anxiety is perhaps one of the most significant current medical and social problems, the neurochemical mechanistic background of this common condition remains to be fully understood. Multifunctional regulatory gasotransmitters are novel, atypical inorganic factors of the brain that are involved in the mechanisms of anxiety responses. Nitric oxide (NO) signaling shows ambiguous action in animal models of anxiety, while NO donors exert anxiogenic or anxiolytic effect depending on their chemical structure, dose, treatment schedule and gas release rapidity. The majority of NO synthase inhibitors act as a relatively potent axiolytic agents, while hydrogen sulfide (H2S) and carbon monoxide (CO) delivered experimentally in the form of “slow” or “fast” releasing donors have recently been considered as anxiolytic neurotransmitters. In this comprehensive review we critically summarize the literature regarding the intriguing roles of NO, H2S and CO in the neuromolecular mechanisms of anxiety in the context of their putative, yet promising therapeutic application. A possible mechanism of gasotransmitter action at the level of anxiety-related synaptic transmission is also presented. Brain gasesous neuromediators urgently require further wide ranging studies to clarify their potential value for the current neuropharmacology of anxiety disorders.

scholarly journals An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Riley Perszyk ◽  
Brooke M Katzman ◽  
Hirofumi Kusumoto ◽  
Steven A Kell ◽  
Matthew P Epplin ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Chemical Structure ◽  
Therapeutic Index ◽  
Allosteric Modulator ◽  
High Potency ◽  
Structural Determinants ◽  
Negative Allosteric Modulator ◽  
Determinants Of Action ◽  
The Brain

N-methyl-d-aspartate receptors (NMDARs) are an important receptor in the brain and have been implicated in multiple neurological disorders. Many non-selective NMDAR-targeting drugs are poorly tolerated, leading to efforts to target NMDAR subtypes to improve the therapeutic index. We describe here a series of negative allosteric NMDAR modulators with submaximal inhibition at saturating concentrations. Modest changes to the chemical structure interconvert negative and positive modulation. All modulators share the ability to enhance agonist potency and are use-dependent, requiring the binding of both agonists before modulators act with high potency. Data suggest that these modulators, including both enantiomers, bind to the same site on the receptor and share structural determinants of action. Due to the modulator properties, submaximal negative modulators in this series may spare NMDAR at the synapse, while augmenting the response of NMDAR in extrasynaptic spaces. These modulators could serve as useful tools to probe the role of extrasynaptic NMDARs.

scholarly journals The Role of Flavonoids on Oxidative Stress in Epilepsy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tâmara Coimbra Diniz ◽  
Juliane Cabral Silva ◽  
Sarah Raquel Gomes de Lima-Saraiva ◽  
Fernanda Pires Rodrigues de Almeida Ribeiro ◽  
Alessandra Gomes Marques Pacheco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Central Nervous System ◽  
Nervous System ◽  
Chemical Structure ◽  
Free Radical Production ◽  
Radical Production ◽  
The Central Nervous System ◽  
The Brain ◽  
Benzodiazepine Site

Backgrounds. Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects.Objective. This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed.Results/Conclusions. There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy.

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

Potential Uses of Vinegar as a Medicine and Related in vivo Mechanisms

2016 ◽  
Vol 86 (3-4) ◽  
pp. 127-151 ◽  
Author(s):  
Zeshan Ali ◽  
Zhenbin Wang ◽  
Rai Muhammad Amir ◽  
Shoaib Younas ◽  
Asif Wali ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Review Paper ◽  
Heart Diseases ◽  
Folk Medicine ◽  
Active Role ◽  
Current Review ◽  
Different Types ◽  
Positive Effect

While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has found that vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates are a good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current review paper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseases both in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

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