The Neuropathology of Concussion

This review provides a detailed analysis of the pathophysiology involved in traumatic brain injury (TBI), with an emphasis on mild TBI and chronic traumatic encephalopathy (CTE). It explains the dynamic interaction between mechanical trauma and the neuroinflammatory response, especially the crucial role of microglia in post-TBI inflammation. Moreover, the review discusses the significance of dendritic and spinal changes as indicators of a regenerative response. The role of transactive response (TAR) DNA-binding protein 43 and tau protein in the pathogenesis of mild TBI and CTE is assessed, with tau protein changes being a potential biomarker for acute and chronic TBI-related conditions. The study also investigates syndromes commonly found in young athletes, such as second impact syndrome and juvenile head trauma syndrome. The review addresses the complex inflammatory response after mild TBI, focusing on pro-inflammatory and anti-inflammatory mediators, including IL-1, IL-6, TNF-α, and CRP as potential indicators of injury severity and outcome. The review calls for further research to elucidate the exact relationship of these factors in TBI and its long-term effects

Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context

PRELIMINARY DATA ON SOME BEHAVIORAL CHANGES INDUCED BY SHORT-TERM INTRAPERITONEAL OXYTOCIN ADMINISTRATION IN AGED RATS

Introduction: Oxytocin (OT) is a well-known neuropeptides which together with vasopressin, melatonin, insulin and other hormones can alter both behavior and physiological or neuronal functions. This growing interest on OT roles is also based on the demonstrated beneficial effects as a stress reliever and a social bonding agent. The association between old age and OT was only vaguely studied. Little or few is known on the effect of the OT hormone on the old body. Hereby, we present our preliminary results in the research on behavioral changes regarding the intraperitoneal administration of OT in aged rats. Subjects and methods: OT was administered for 8 days in Wistar aged rats in parallel with saline administration for control group. Behavioral markers were assessed in some specific behavioral tasks, such as the Y-Maze test for short-term working memory, Open Field test, Elevated Plus Maze, and Forced Swim test for anxious and depressive behavior assessment, and Three-chambered Maze test for sociability assessment. Results: Increased mobility and decreased anxiety behaviors were reported for the aged intraperitoneal OT-treated animals, as compared with controls, during FST and OFT, and respectively FST, EPM, and OFT. Also, decreased depressive-like behaviors were observed in the same animal group during FST and ST. Moreover, a decrease in anxiolytic behavior was observed as exposed to stressful stimuli (such as grooming behavior in OFT, and forced grooming behavior in ST), and as exposed to social stimuli (such as grooming behavior in TCT). Similarly, significant differences were obtained regarding the social behavior of the intraperitoneal OT-treated animal as compared to control group, the animals showing increased sociability and social preference for the stranger animal in TCT. However, no significant effects on the working memory (assessed as spontaneous alternation in YMT) were observed. Conclusions: Intraperitoneal administration of OT in aged rats has clear effects on anxious and depressive behavior, but no significant effects on the working memory. Also, several beneficial effects of OT on social preferences and sociability were observed

CURRENT STATUS OF RESEARCH ON TRANSGENIC ANIMAL MODELS FOR ALZHEIMER’S DISEASE

Each and every pathological visible effect is mostly due to molecular or biochemical reactions on cellular and intracellular level. This was the reason why in the last decade many incurable or poorly understood diseases were at least partially described. This is also the Alzheimer’s disease case, extremely aggressive and highly unpredictable. Many studies showed various conclusions used in further research to develop treatments and biochemical therapies in order to slow the degenerative effects or to eradicate the means and motives of this disease. Generally, in order to cure a certain disease, one must surely know the mechanisms of actions involved in its pathology and the start point, also very important. In Alzheimer’s disease, there has been studied an entire cohort of hypothesis and by using animal models the researchers reached possible cause variants. Because of the unknown idiopathic Alzheimer’s disease etiology, animal models were based on genetic mutations associated with familial Alzheimer, supposing that following events are identical. These genetic models are highly valuable to elucidate the molecular mechanisms which determine the disease’s progression, although no animal model can replicate the entire disease symptomatology. For this reason, every animal model type can be used to study one aspect of the disease. For example, transgenic mice overexpressing APP gene exhibit a similar pathology as humans. Age dependence and beta-amyloid accumulation speed was determined also by using transgenic mice. Beta-amyloid plaques discovered in transgenic mice brains were extremely similar to humans ones. Using the same manner of research, it was found a link between beta-amyloid plaques and alfa-synuclein. Plaques coloring method was also developed by various coloring techniques used on histological transgenic mice brain tissue smears. Alzheimer’s disease pathology was well studied using transgenic animal models in order to characterize the molecular deficiencies observed in humans. Because of the incapacity of study on human subjects due to ethical reasons and specific human characteristics, several animal models have been developed, which facilitated the study Alzheimer’s disease features one at a time

BASIC ASPECTS IN SELECTING A SUITABLE TRANSGENIC RODENT MODEL FOR ALZHEIMER’S DISEASE

Due to Alzheimer’s disease (AD) great aggressiveness, many worldwide health associations began to globalize research efforts in order to find a suitable treatment and to clarify once and for all its controversial aetiology. Moreover, the animal modelling research is one of the best tools to evaluate molecular mechanisms and to correlate them with clinical features and behaviours. However, in order to provide valuable scientific data correlated to low error sources, a rigorous algorithm of selecting the proper animal model for testing is required. An ideal animal model for AD research has probably not yet been developed, but by a careful selection of the existent models or even by developing new models suitable to research conditions, consistent progress in this area of research can be achieved. This paper aims to show and centralize some of the valuable information gathered along the past years of failure and success in Alzheimer’s disease animal modelling, in order to provide a theoretical ground for new and innovative aspects in this rather new area of research

Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as “irritable bowel syndrome”, “gut brain axis”, “oxidative stress”, “neuroendocrine”, and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development

CURRENT STATUS OF KNOWLEDGE ON ALZHEIMER’S DISEASE GENETICS

As the entire human being works as a perfectly balanced whole, each and every disturbance at any level brings other disturbances, like a chain reaction to superior levels, the current researches aim for the molecular aspects of any physiological disorders. It is well possible that any physiological reaction is not the cause of a disease but an effect of molecular disturbances in biochemical and genetic mechanisms responsible for a feature or behavior exhibit. The exact causes of Alzheimer’s disease are mostly unknown, excepting 1 to 5% cases notably identified with obvious genetic variance. In the scientific world, there are many hypotheses that explain the occurrence of Alzheimer’s disease: amyloidal hypothesis, taupathy hypothesis, cholinergic hypothesis and so on, but from all of these it seems that the molecular/genetic hypothesis is the most studied of all, because of its relevance to the true pathological mechanism. It seems that some allelic variants and mutations of genes that encode important regulatory molecules in neuronal activity may give a certain predisposition to Alzheimer’s disease or to other neurodegenerative diseases, even in young individuals. One good example is the APOE gene that encodes a surface component of triglyceride reach lipoproteins. At the neuronal level, this glycoprotein has an important role in lipid distribution during nerves growth and repair. The APOE gene exists in three allele variants present in human population in different proportions (ε2, ε3, ε4) which in different combinations give to the carrier various predispositions to cholesterol and triglycerides mechanisms disorders, Levy’s bodies dementia and Alzheimer’s disease (ε4 allele

Biomolecules from Plant Wastes Potentially Relevant in the Management of Irritable Bowel Syndrome and Co-Occurring Symptomatology

During and following the processing of a plant’s raw material, considerable amounts are wasted, composted, or redistributed in non-alimentary sectors for further use (for example, some forms of plant waste contribute to biofuel, bioethanol, or biomass production). However, many of these forms of waste still consist of critical bioactive compounds used in the food industry or medicine. Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. The primary treatment is based on symptomatology alleviation and controlled dietary management. Thus, this review aimed to describe the possible relevance of molecules residing in plant waste that can be used to manage IBS and co-occurring symptoms. Significant evidence was found that many forms of fruit, vegetable, and medicinal plant waste could be the source of some molecules that could be used to treat or prevent stool consistency and frequency impairments and abdominal pain, these being the main IBS symptoms. While many of these molecules could be recovered from plant waste during or following primary processing, the studies suggested that enriched food could offer efficient valorization and prevent further changes in properties or stability. In this way, root, stem, straw, leaf, fruit, and vegetable pomaces were found to consist of biomolecules that could modulate intestinal permeability, pain perception, and overall gastrointestinal digestive processes

A Systematic Review and Meta-Analysis of the Inflammatory Biomarkers in Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite its high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI has been previously provided. Thus, this systematic review and meta-analysis aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. In this regard, eight studies comprising 1184 individuals were selected. Thus, it was shown that the increase in IL-6, TNF-α, and IL-1β plasma levels could be implicated in the development of early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI

Interactions between Sleep and Emotions in Humans and Animal Models

Recently, increased interest and efforts were observed in describing the possible interaction between sleep and emotions. Human and animal model studies addressed the implication of both sleep patterns and emotional processing in neurophysiology and neuropathology in suggesting a bidirectional interaction intimately modulated by complex mechanisms and factors. In this context, we aimed to discuss recent evidence and possible mechanisms implicated in this interaction, as provided by both human and animal models in studies. In addition, considering the affective component of brain physiological patterns, we aimed to find reasonable evidence in describing the two-way association between comorbid sleep impairments and psychiatric disorders. The main scientific literature databases (PubMed/Medline, Web of Science) were screened with keyword combinations for relevant content taking into consideration only English written papers and the inclusion and exclusion criteria, according to PRISMA guidelines. We found that a strong modulatory interaction between sleep processes and emotional states resides on the activity of several key brain structures, such as the amygdala, prefrontal cortex, hippocampus, and brainstem nuclei. In addition, evidence suggested that physiologically and behaviorally related mechanisms of sleep are intimately interacting with emotional perception and processing which could advise the key role of sleep in the unconscious character of emotional processes. However, further studies are needed to explain and correlate the functional analysis with causative and protective factors of sleep impairments and negative emotional modulation on neurophysiologic processing, mental health, and clinical contexts