Neuromodulators and its combinations for the preventive treatment of migraine

2011 ◽  
pp. 173-181
Author(s):  
Abouch Valenty Krymchantowski ◽  
Carla da Cunha Jevoux

Migraine is a chronic, debilitating neurological disorder. It affects nearly 15% of the adult population and it is characterized by a range of symptom profiles and degrees of disability. It is a disease generally believed to occur in consequence of a genetically hyper excitable brain state, in addition to a neurotransmitter dysfunction which results in susceptibility to the occurrence of intermittent attacks of headache with particular associated features. Pharmacotherapy remains the mainstay for the prevention of the attacks and despite the use of different classes of drugs, some older than 30 years and used by serendipity, some neuromodulators represent the most modern option and the better studied drugs for the prophylactic treatment of migraine. Supposedly acting by targeting one or more molecular sites in the brain, these drugs alter neurotransmission through effects on ion channels, on specific receptors and on neurotransmitter metabolism. Neuromodulators are considered the state of art in migraine therapeutic and its combination may represent an upcoming option for patients not responding well or presenting limiting tolerability issues with full-dose monotherapy. In this review, we explore the specificities of the different drugs belonging to this pharmacological class, the evidence available for its use in migraine as well as the fundamentals and potential for new approaches combining two neuromodulators, even in lower doses.

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.


2021 ◽  
Vol 22 (7) ◽  
pp. 3330
Author(s):  
Mehdi Eshraghi ◽  
Aida Adlimoghaddam ◽  
Amir Mahmoodzadeh ◽  
Farzaneh Sharifzad ◽  
Hamed Yasavoli-Sharahi ◽  
...  

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.


Author(s):  
Alexander Gordon ◽  
◽  
Daniel Lashley ◽  
Stuart Weatherby ◽  
◽  
...  

Headaches make up 30% of all Neurology outpatient consultations.1 There is distinct variability in the management of headaches by Neurologists, leading to unnecessary disparities in the standard of care and likelihood of response between patients. A significant proportion of patients with headache diagnoses do not receive the evidence-based treatments recommended in national or international guidelines,2 and substantial numbers of patients are not receiving preventive therapies.3  Ziegeler et al. found that a third of patients reporting to a tertiary headache centre had not received preventive therapy in line with guidelines, and half had never been prescribed a preventive treatment.2 Considering that 46% of the global adult population are estimated to have a headache disorder,4 this lack of a consistent, evidence-based approach is somewhat incongruent with the patient socio-economic impact. It is probable that lack of adherence to current headache guidelines is a multi-faceted issue. This variation in treatment (and therefore patient outcome), although unexplored,2 is not likely to be a simple educational issue. To add to this, an educational approach, in the form of seminars and workshops, does not have entirely positive evidence to support its use in implementing changes to patient care.5  It seems more probable that there are also structural issues within the health service that in some way preclude patients with headache disorders from gaining appropriate care.  For example, using only doctors to care for patients with such a common condition may cause bottle-necking in access, and may not be an appropriate use of clinical resource.  The current context of a global pandemic has shown us the importance of using the skillsets of all NHS staff working together for patient care.  For headache care this could involve greater use of nursing colleagues or allied health professionals such as Pharmacists. To facilitate such an aim, an easily used and standardised approach is essential. We believe that the guidelines from the British Association for the Study of Headache (BASH),6 could facilitate such an approach.


2021 ◽  
Author(s):  
S. R. Stockdale ◽  
L. A. Draper ◽  
S. M. O’Donovan ◽  
W. Barton ◽  
O. O’Sullivan ◽  
...  

AbstractParkinson’s disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into Lewy body aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes a potential trigger initiating the misfolding of α-syn. However, changes in the gut virome in response to α-syn alterations have not been investigated. In this study, we show longitudinal changes in the faecal virome of rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn. The virome β-diversity changes after α-syn treatment were compounded by the addition of LPS as an adjunct. Changes in the diversity of rat faecal viromes were observed after one month and did not resolve within the study’s five month observational period. Overall, these results suggest that microbiome alterations associated with PD may, partially, be reactive to host α-syn associated changes.


Author(s):  
Dr. Priyanka Kandikattiwar

ABSTRACT:- It is common lifelong health disease. India had more diabetics than any other country in the world, according to the International Diabetes Foundation, although the country has now been surpassed in the top spot by China. Diabetes currently affects more than 62 million Indians, which is more than 7.1% of the adult population. The average age on onset is 42.5 years. Nearly 1 million Indians die due to diabetes every year1. According to WHO Diabetes is a Life style disorder. The main cause of diabetes is there is restless lifestyle, stress, unnatural dietary factor. It has turned out biggest silent killer today’s in world. In Ayurveda diabetes can be correlated with Madhumeh which is a Vata predominant disease. Causes of Madhumeh are Diwaswap, Atyaambupan(excessive water intake), Guru, Madhur, Shita, Snighatdh, Ahara Sevan2 etc. Now a day most of people think drinking large amounts of water is helpful for proper skin health, Digestion, and Health, etc? Claims have been made that excessive drinking water gives you a radiant skin, and healthy while others people say it has no effect and it causes many disease and side effect .so here is effort to highlight the Atyambupan (Excessive water intake) as Nidan of Diabetes given in Ayurvedic text as well as occurring at present and make aware the society to prevent the disease through Nidanparivarjan.


2019 ◽  
Author(s):  
Jarno Tuominen ◽  
Sakari Kallio ◽  
Valtteri Kaasinen ◽  
Henry Railo

Can the brain be shifted into a different state using a simple social cue, as tests on highly hypnotisable subjects would suggest? Demonstrating an altered brain state is difficult. Brain activation varies greatly during wakefulness and can be voluntarily influenced. We measured the complexity of electrophysiological response to transcranial magnetic stimulation (TMS) in one “hypnotic virtuoso”. Such a measure produces a response outside the subject’s voluntary control and has been proven adequate for discriminating conscious from unconscious brain states. We show that a single-word hypnotic induction robustly shifted global neural connectivity into a state where activity remained sustained but failed to ignite strong, coherent activity in frontoparietal cortices. Changes in perturbational complexity indicate a similar move toward a more segregated state. We interpret these findings to suggest a shift in the underlying state of the brain, likely moderating subsequent hypnotic responding. [preprint updated 20/02/2020]


1999 ◽  
Vol 7 ◽  
pp. 63-67
Author(s):  
S.C. Munday-Finch ◽  
I. Garthwaite

The ryegrass endophyte/plant interaction produces a number of toxic metabolites responsible for a range of toxicoses including ryegrass staggers. Although lolitrem B has long been considered the toxin responsible for ryegrass staggers in farm animals, it is only recently that we have demonstrated that oral administration of the pure toxin causes tremors in mice consistent with the symptoms of ryegrass staggers. Various levels of the toxin were incorporated into the diet of mice and tremor response measured regularly. Mice were very susceptible to the tremorgenic action of lolitrem B with a dose of only 1.1 mg/kg per day being sufficient to induce a tremor response. Analysis of faeces from a dosed mouse showed that approximately 40% of the toxin ingested was excreted unchanged. The profile of tremor response shows that tremors build up over a 24-hour period and then reach a dose dependent plateau suggesting that toxin turnover reaches a steady state. In experiments designed to test the possibility that tremorgens bind to specific receptors in the brain, mice were injected with the 14C-labelled tremorgen, paxilline. Paxilline was chosen as it is similar in structure and possible action to lolitrem B and could be more easily prepared with an isotopic label. Following injection of 14C-paxilline to mice their brains and spinal cord were sectioned and analysed for 14C content. Localised binding was not detected but rather an even distribution of isotope was observed. This is probably due to the lipophilicity of the tremorgens, which distribute randomly throughout the fatty brain matrix, masking any binding to specific regions or receptors. This study showed, however, that only a minute proportion of the administered tremorgen reached the brain and spinal cord, indicating that, if this is the site of action, the receptors involved in the initiation of staggers are extremely sensitive to the tremorgens. Keywords: endophyte, lolitrem, Lolium perenne, mycotoxin, Neotyphodium lolii, neurotoxin, oral dosing, ryegrass staggers, tremor, tremorgen


Author(s):  
M. P. Butko ◽  
◽  
P. A. Popov ◽  
D. A. Onishchenko ◽  
◽  
...  

The article provides an overview of the drugs used for disinfection in poultry farming (perepelovodstve) and the results of using Hyponate-BPO for the prophylactic treatment of premises and cells intended for quail maintenance.


Author(s):  
M. Atif Yaqub ◽  
Keum-Shik Hong ◽  
Amad Zafar ◽  
Chang-Seok Kim

Transcranial direct current stimulation (tDCS) has been shown to create neuroplasticity in healthy and diseased populations. The control of stimulation duration by providing real-time brain state feedback using neuroimaging is a topic of great interest. This study presents the feasibility of a closed-loop modulation for the targeted functional network in the prefrontal cortex. We hypothesize that we cannot improve the brain state further after reaching a specific state during a stimulation therapy session. A high-definition tDCS of 1[Formula: see text]mA arranged in a ring configuration was applied at the targeted right prefrontal cortex of 15 healthy male subjects for 10[Formula: see text]min. Functional near-infrared spectroscopy was used to monitor hemoglobin chromophores during the stimulation period continuously. The correlation matrices obtained from filtered oxyhemoglobin were binarized to form subnetworks of short- and long-range connections. The connectivity in all subnetworks was analyzed individually using a new quantification measure of connectivity percentage based on the correlation matrix. The short-range network in the stimulated hemisphere showed increased connectivity in the initial stimulation phase. However, the increase in connection density reduced significantly after 6[Formula: see text]min of stimulation. The short-range network of the left hemisphere and the long-range network gradually increased throughout the stimulation period. The connectivity percentage measure showed a similar response with network theory parameters. The connectivity percentage and network theory metrics represent the brain state during the stimulation therapy. The results from the network theory metrics, including degree centrality, efficiency, and connection density, support our hypothesis and provide a guideline for feedback on the brain state. The proposed neuro-feedback scheme is feasible to control the stimulation duration to avoid overdosage.


Author(s):  
Joseph Levine

There are two basic philosophical problems about colour. The first concerns the nature of colour itself. That is, what sort of property is it? When I say of the shirt that I am wearing that it is red, what sort of fact about the shirt am I describing? The second problem concerns the nature of colour experience. When I look at the red shirt I have a visual experience with a certain qualitative character – a ‘reddish’ one. Thus colour seems in some sense to be a property of my sensory experience, as well as a property of my shirt. What sort of mental property is it? Obviously, the two problems are intimately related. In particular, there is a great deal of controversy over the following question: if we call the first sort of property ‘objective colour’ and the second ‘subjective colour’, which of the two, objective or subjective colour, is basic? Or do they both have an independent ontological status? Most philosophers adhere to the doctrine of physicalism, the view that all objects and events are ultimately constituted by the fundamental physical particles, properties and relations described in physical theory. The phenomena of both objective and subjective colour present problems for physicalism. With respect to objective colour, it is difficult to find any natural physical candidate with which to identify it. Our visual system responds in a similar manner to surfaces that vary along a wide range of physical parameters, even with respect to the reflection of light waves. Yet what could be more obvious than the fact that objects are coloured? In the case of subjective colour, the principal topic of this entry, there is an even deeper puzzle. It is natural to think of the reddishness of a visual experience – its qualitative character – as an intrinsic and categorical property of the experience. Intrinsic properties are distinguished from relational properties in that an object’s possession of the former does not depend on its relation to, or even the existence of, other objects, whereas its possession of the latter does. Categorical properties are distinguished from dispositional ones. A dispositional property is one that an object has by virtue of its tendency to behave in certain ways, or cause certain effects, in particular circumstances. So being brittle is dispositional in that it involves being liable to break under slight pressure, whereas being six feet tall, say, is categorical. If subjective colour is intrinsic and categorical, then it would seem to be a neural property of a brain state. But what sort of neural property could explain the reddishness of an experience? Furthermore, reduction of subjective colour to a neural property would rule out even the possibility that forms of life with different physiological structures, or intelligent robots, could have experiences of the same qualitative type as our experiences of red. While some philosophers endorse this consequence, many find it quite implausible. Neural properties seem best suited to explain how certain functions are carried out, and therefore it might seem better to identify subjective colour with the property of playing a certain functional role within the entire cognitive system realized by the brain. This allows the possibility that structures physically different from human brains could support colour experiences of the same type as our own. However, various puzzles undermine the plausibility of this claim. For instance, it seems possible that two people could agree in all their judgements of relative similarity and yet one sees green where the other sees red. If this ‘inverted spectrum’ case is a genuine logical possibility, as many philosophers advocate, then it appears that subjective colour must not be a matter of functional role, but rather an intrinsic property of experience. Another possibility is that qualitative character is just a matter of features the visual system, in the case of colour, is representing objects in the visual field to have. Reddish experiences are just visual representations of red. But this view too has problems with spectrum-inversion scenarios, and also entails some counterintuitive consequences concerning our knowledge of our own qualitative states. Faced with the dilemmas posed by subjective colour for physicalist doctrine, some philosophers opt for eliminativism, the doctrine that subjective colour is not a genuine, or real, phenomenon after all. On this view the source of the puzzle is a conceptual confusion; a tendency to extend our judgements concerning objective colour, what appear to be intrinsic and categorical properties of the surfaces of physical objects, onto the properties of our mental states. Once we see that nothing qualitative is happening ‘inside’, we will understand why we cannot locate any state or property of the brain with which to identify subjective colour. The controversy over the nature of subjective colour is part of a wider debate about the subjective aspect of conscious experience more generally. How does the qualitative character of experience – what it is like to see, hear and smell – fit into a physicalist scientific framework? At present all of the options just presented have their adherents, and no general consensus exists.


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