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Topic Review
The Gut-Immune-Brain Axis in Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic inflammatory disease comprising two major clinical entities—Crohn’s disease (CD) and ulcerative colitis (UC). IBD incidence remains constantly high in industrialized countries and continuously rises in emerging economies. Importantly, IBD is associated with neuropsychiatric symptoms that strongly worsen IBD disease burden. Mounting evidence indicates that chronic gut inflammation induces a systemic immune response that might cause the CNS manifestation in IBD. In line with this, biologicals targeting inflammatory circuits exerted robust positive effects on depressive symptoms in many autoimmune diseases, and in IBD in particular. Therefore, research in recent years increasingly focused on the characterization of local and systemic immune reactions in IBD, and on entry routes of inflammatory cells and molecules into the CNS. The ultimate aim is to understand how the changes in the neuroimmune landscape impair the function of neurons to cause neuropsychiatric symptoms. In addition, the role of intestinal microbiota in the gut–immune–brain axis in IBD will be discussed. 
  • 1.5K
  • 18 Oct 2022
Topic Review
Ursolic and Oleanolic Acids
Ursolic and oleanolic acids are secondary plant metabolites that are known to be involved in the plant defence system against water loss and pathogens. Nowadays these triterpenoids are also regarded as potential pharmaceutical compounds, compounds or triterpenoid-enriched plant extracts exert various beneficial effects, including anti-oxidative, anti-inflammatory and anticancer, on model systems of both human or animal origin. Some of those effects have been linked to the ability of ursolic and oleanolic acids to modulate intracellular antioxidant systems and also inflammation and cell death-related pathways.
  • 1.5K
  • 07 May 2021
Topic Review
Visual Hallucinations in Migraine and Epilepsy
Since the earliest descriptions of the simple visual hallucinations in migraine patients and in subjects suffering from occipital lobe epilepsy, several important issues have arisen in recognizing epileptic seizures of the occipital lobe, which often present with symptoms mimicking migraine. A detailed quantitative and qualitative clinical scrutiny of timing and characteristics of visual impairment can contribute to avoiding mistakes. Differential diagnosis, in children, might be challenging because of the partial clinical, therapeutic, and pathophysiological overlaps between the two diseases that often coexist. Ictal elementary visual hallucinations are defined by color, shape, size, location, movement, speed of appearance and duration, frequency, and associated symptoms and their progression. The evaluation of the distinctive clinical features of visual aura in migraine and visual hallucinations in occipital epilepsy could contribute to understanding the pathogenetic mechanisms of these two conditions. 
  • 1.5K
  • 04 May 2023
Topic Review
Approaches to Estimate Minimum Clinically Important Differences
The origin of evidence-based medicine (EBM) dates back to the 1970s. This paradigm emphasizes a methodical evaluation of the evidence for use in health care decision-making, along with the knowledge of decision-makers and the expectations and values of patients. There is a growing awareness of correlating statistically significant results with clinical relevance in clinical trials to avoid the misinterpretation of study findings and prevent patients from being exposed to unnecessary therapies. The concept of “clinically important difference”, which has been developed as a way to overcome the drawbacks of a “statistically significant difference” and which represents a change that the patient feels, is noteworthy. The minimum clinically important difference (MCID) is the threshold value for such a change, first described by Jaeschke and colleagues in 1989. There has been a shift towards considering clinical relevance rather than just statistical significance in interpreting results from clinical trials. Multiple rating scales, such as the Modified Rankin Scale (mRS) and the Barthel Index (BI), are commonly used as outcome measures in both daily neurological practice and clinical trials, including stroke trials.
  • 1.5K
  • 18 Jan 2024
Topic Review
The Effects of Diets on the “Gut–Brain” Pathways
With depression becoming increasingly prevalent, being closely associated with stress, and many patients exhibiting resistance to current treatments, depression pathophysiology requires further elucidation. Recent research has shown complex bidirectional links between the brain and the gut, and the gut microbiota and the influence of diet is beginning to provide new clues to the complex nature of this disorder. It is well known that diet is a key modulator of gut microbial composition. In humans, good quality plant-based diets such as the Mediterranean diet have been shown to reduce pathogenic bacteria in the gut, increase Bifidobacterium and Clostridium, as well as lower the risk of depression, while poorer quality diets such as the Western diet have been shown to reduce Lactobacillus in the gut, reduce overall gut microbial diversity and have been associated with increased depression risk. Evaluating the effects of diets on the brain-to-gut and gut-to-brain mechanisms in animal models of stress and depression may aid in the elucidation of the pathophysiology of depression and may provide novel therapeutic approaches. 
  • 1.5K
  • 21 Feb 2022
Topic Review
Molecular Mechanisms Responsible for Altered Mitostasis in ALS
Amyotrophic lateral sclerosis (ALS) is a fatal multisystem disease characterized by progressive death of motor neurons, loss of muscle mass, and impaired energy metabolism. The morphology and dynamics of mitochondrial network, quality control mechanisms, motility, and overall mitochondrial function are closely interrelated pathways that play a fundamental role in the dyshomeostasis of mitochondria in neurons, surrounding glial cells, myocytes, and many other cell types across peripheral tissues. Molecular mechanisms responsible for altered mitostasis in ALS-affected cells contribute to excitotoxicity, oxidative stress, energy deficiency and, ultimately, the death of motoneurons and other cells. Damaged mitochondria can release a number of proapoptotic factors and inflammatory response activators called damage-related molecular patterns, which creates a cycle of direct communication between mitochondrial disorders, inflammation, and cell degeneration.
  • 1.5K
  • 19 Dec 2023
Topic Review
Picein
Picein is a herbal agent that has been investigated in only a few studies. Picein is the active ingredient of several herbs and can thus be extracted from different types of plants, which renders it widely available. To date, picein has shown to exhibit antioxidant and anti-inflammatory properties in cellular and plant studies.
  • 1.5K
  • 31 Oct 2022
Topic Review
Fenamates for Neurodegenerative Disorders
Neurodegenerative disorders are desperately lacking treatment options. It is imperative that drug repurposing be considered in the fight against neurodegenerative diseases. Fenamates have been studied for efficacy in treating several neurodegenerative diseases. 
  • 1.5K
  • 06 May 2021
Topic Review
Cell Autonomous Mechanisms in Astrocytes in Neurodegenerative Diseases
Neurodegenerative disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) affect millions of people worldwide, and as the average human lifespan increases, similarly grows the number of patients. Cognitive and motoric decline has been explained by the very apparent deterioration of neurons in various regions of the brain and spinal cord. However, more studies show that disease progression is greatly influenced by the vast population of glial cells. Astrocytes are traditionally considered star-shaped cells on which neurons rely heavily for their optimal homeostasis and survival. Increasing amounts of evidence depict how astrocytes lose their supportive functions while simultaneously gaining toxic properties during neurodegeneration. 
  • 1.5K
  • 12 Mar 2024
Topic Review
Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase
Parkinson’s disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD.
  • 1.5K
  • 15 Apr 2022
Topic Review
Uncoupling Proteins for Neurodegenerative Diseases
Most of the major retinal degenerative diseases are associated with significant levels of oxidative stress. One of the major sources contributing to the overall level of stress is the reactive oxygen species (ROS) generated by mitochondria. The driving force for ROS production is the proton gradient across the inner mitochondrial membrane. This gradient can be modulated by members of the uncoupling protein family, particularly the widely expressed UCP2. The overexpression and knockout studies of UCP2 in mice have established the ability of this protein to provide neuroprotection in a number of animal models of neurological disease, including retinal diseases. The expression and activity of UCP2 are controlled at the transcriptional, translational and post-translational levels, making it an ideal candidate for therapeutic intervention. 
  • 1.5K
  • 30 Jun 2022
Topic Review
Neurofibromatosis and Schwannomatosis
Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of all cases, NF2 in 3%, and schwannomatosis (SWN) in <1%. The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras/MAPK and PI3K/mTOR signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to ezrin-radixin-moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of SWN remain unclear. Inactivating mutations in the tumor suppressor genes SMARCB1 and LZTR1 are considered responsible for a majority of cases.
  • 1.5K
  • 08 Jun 2021
Topic Review
Mechanisms of Pain Modulation
A review of the pathophysiology of pain and its treatment, from a surgical point of view has been published (Sola RG, Pulido P. Neurosurgical Traatment of Pain. Brain Sci. 2022, 12(11), 1584; https://doi.org/10.3390/brainsci12111584) There are pain syndromes of difficult medical control.In these cases, surgical treatment may be an excellent alternative. The bases on which the different surgical approaches are based are described. The attached table shows a very schematic view of the neurosurgical treatment of pain.      
  • 1.5K
  • 22 Jan 2023
Topic Review
Myotonia Congenita
Myotonia congenita (MC) is a rare disorder characterized by stiffness and weakness of the limb and trunk muscles. Mutations in the SCN4A gene encoding the alpha-subunit of the voltage-gated sodium channel Nav1.4 have been reported to be responsible for sodium channel myotonia (SCM). The Nav1.4 channel is expressed in skeletal muscles, and its related channelopathies affect skeletal muscle excitability, which can manifest as SCM, paramyotonia, and periodic paralysis. In this study, the missense mutation p.V445M was identified in two individual families with MC. To determine the functional consequences of having a mutated Nav1.4 channel, whole-cell patch-clamp recording of transfected Chinese hamster ovary cells was performed. Evaluation of the transient Na+ current found that a hyperpolarizing shift occurs at both the activation and inactivation curves with an increase of the window currents in the mutant channels. The Nav1.4 channel’s co-expression with the Navβ4 peptide can generate resurgent Na+ currents at repolarization following a depolarization. The magnitude of the resurgent currents is higher in the mutant than in the wild-type (WT) channel. Although the decay kinetics are comparable between the mutant and WT channels, the time to the peak of resurgent Na+ currents in the mutant channel is significantly protracted compared with that in the WT channel. These findings suggest that the p.V445M mutation in the Nav1.4 channel results in an increase of both sustained and resurgent Na+ currents, which may contribute to hyperexcitability with repetitive firing and is likely to facilitate recurrent myotonia in SCM patients.
  • 1.5K
  • 29 Oct 2020
Topic Review
Antimyostatin Treatment
Myostatin, also known as growth and differentiation factor 8 (GDF-8), was identified in 1997 by McPherron and Lee.
  • 1.5K
  • 09 Jun 2021
Topic Review
Tryptophan Dysmetabolism and Quinolinic Acid in Neurodegenerative Diseases
Evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role in pathogenesis, is one of several competing pathways of tryptophan metabolism. A disturbed tryptophan metabolism with increased activity of the kynurenine pathway and production of quinolinic acid may result in deficiencies in tryptophan and derived neurotransmitters. Quinolinic acid is an N-methyl-D-aspartate receptor agonist, and raised levels in CSF, together with increased levels of inflammatory cytokines, have been reported in mood disorders. Increased quinolinic acid has also been observed in neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and HIV-related cognitive decline. 
  • 1.5K
  • 29 Jul 2022
Topic Review
Psychophysiological perspectives on emotion regulation
Several studies have suggested a correlation between heart rate variability (HRV), emotion regulation (ER), and consequent psychopathological conditions. Specifically, recent data seem to support the hypothesis that low-frequency heart rate variability (LF-HRV), an index of sympathetic cardiac control, correlates with worse ER and specific psychopathological dimensions. The present work aims to review the previous findings on these topics and integrate them from two main cornerstones of this perspective: Porges’ Polyvagal Theory and Thayer and Lane’s Neurovisceral Integration Model, which are necessary to understand these associations better. For this reason, based on these two approaches, we point out that low HRV is associated with emotional dysregulation and transversal psychopathological conditions. This understanding is beneficial as a theoretical ground from which to start for further research studies and as a starting point for new theoretical perspectives useful in clinical practice. 
  • 1.5K
  • 22 Sep 2021
Topic Review
Salt Intake
Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic sodium (Na) intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin–angiotensin–aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. 
  • 1.5K
  • 15 Feb 2023
Topic Review
Brain Lesion Theory
The term Brain lesion theory is a colloquialism which generally refers to the idea that brain lesions and traumatic brain injury are associated with aggressive and violent behaviour, criminality and anti-sociality . The concept of a correlation between brain injury and violent or aggressive behaviour has a strong basis in scientific literature and has been explored across multiple disciplines including forensics, psychology and sociology. Most findings in psychology suggest that the correlation between brain injury and aggression is specific to frontal lobe injury. There’s is little evidence to suggest that damage to other areas of the brain correlates with aggression. The correlations between frontal lobe injury and aggression have important implications in terms of function localisation in the brain. Function localisation is the idea that certain functions are specific certain areas of the brain. There is evidence to suggest that the frontal lobe is responsible for the control of cognitive skills like judgment and emotion regulation. Consequently, damage to the frontal lobe may lead to loss of control and impairment in social/emotional judgement therefore reducing a person’s ability to inhibit negative emotion and as a consequence increase aggressive responses. However, it is important to note that the evidence for a correlation between frontal lobe injury and aggression is heavily based on case study and consequently cannot be used to imply a causal factor in either direction. Further, aggression, violence and anti-sociality also correlate with alcoholism, abuse and a number of psychological, environmental and biological factors thus even if there was evidence for a causal link between brain injury and aggression it cannot be concluded that brain injury alone causes aggression.
  • 1.5K
  • 01 Dec 2022
Topic Review
Xenopus Oocytes to Study Fully-Processed Membrane Proteins
The use of Xenopus oocytes in electrophysiological and biophysical research constitutes a long and successful story, providing major advances to the knowledge of the function and modulation of membrane proteins, mostly receptors, ion channels, and transporters. These cells are capable of correctly expressing heterologous proteins after injecting the corresponding mRNA or cDNA. The Xenopus oocyte has become an outstanding host–cell model to carry out detailed studies on the function of fully-processed foreign membrane proteins after their microtransplantation to the oocyte. 
  • 1.5K
  • 24 Oct 2022
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