Patients' and caregivers' attitudes towards patient assisted suicide or euthanasia in amyotrophic lateral sclerosis-a meta-analysis.

Assisted suicide and euthanasia are long debated topics in amyotrophic lateral sclerosis (ALS) patients care. We conducted a meta-analysis to evaluate the attitudes of ALS patients and their caregivers toward physician-assisted suicide (PAS) and euthanasia. Also, we were interested to identify the factors associated with the positive or negative attitude of patients and caregivers towards PAS/euthanasia. A thorough search of the online databases (PubMed, Cochrane Library, and Web of Science) was conducted and eligibility criteria according to the PRISMA guidelines were used to include the studies in the current meta-analysis. The assessment of the quality of the selected studies was carried out using a pre-specified set of criteria by Cochrane. The studies that were selected for this meta-analysis suggested that the expression of the wish to die is more likely correlated with depression, anxiety, hopelessness, and lack of optimism. The overall prevalence of considering PAS/euthanasia significantly varies in a dependent manner over the cultural, legal, and societal factors. In this context, we found that the opinion on this topic can be deeply personal and may vary widely among individuals and communities. Lower quality of life and lower religiosity were associated with a positive attitude toward PAS/euthanasia. On the other hand, patients who are more religious are less likely to choose PAS/euthanasia. Gender does not appear to play a significant role in determining attitudes towards PAS/euthanasia in ALS patients. Other factors, such as education and psychological state, could also be important. In conclusion, end-of-life decisions in ALS patients are complex and require careful consideration of individual values, beliefs, and preferences. Understanding the factors that influence a patient's attitude towards PAS/euthanasia can help healthcare providers to offer appropriate care and support for these patients and their families.

The Effect of Antipsychotics on Cognition in Schizophrenia-A Current Narrative Review.

The majority of schizophrenia-affected individuals display deficiencies in multiple cognitive domains such as attention, working memory, long-term memory, and learning, deficiencies that are stable throughout the disease. The purpose of this narrative review was to examine the effect of antipsychotics on several cognitive domains affected by schizophrenia. Methods: We searched MEDLINE, Elsevier, Scopus, and DOAJ databases for randomized controlled trials and other studies investigating the effects of typical and atypical antipsychotics on cognition in patients with schizophrenia in studies conducted in the last decade. Results: The majority of studies included in this review showed that antipsychotics (especially SGAs) have positive effects on both cognition and general psychopathology of schizophrenia. We mention that treatment with antipsychotic substances represents an ongoing effort of the researchers, who are constantly searching for the best approach to meet the mental health needs of schizophrenia patients. Conclusions: Even with those positive results, it should be noted that more studies are needed in order to fully observe the various effects of certain antipsychotic substances on cognition.

A narrative review of risk factors and predictors for poor outcome and prolonged recovery after a mild traumatic brain injury.

Mild traumatic brain injuries (mTBI) are often caused by a blow to the head or a sudden jolt resulting in a wide range of physical, cognitive, and emotional temporary symptoms. Mild TBI diagnosis can be challenging and most commonly followed by post-concussion syndrome (PCS). When the symptoms are present for more than 3 months, prolonged post-concussive syndrome (PPCS) can be suspected. This review aims to identify and summarize the current status of the knowledge regarding the risk factors and predictors of the recovery from PCS and PPCS. A comprehensive search of the main scientific databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed using keywords, such as: 'prolonged post-concussion syndrome', combined with 'risk factors', 'predictors', and 'outcomes'. Multiple studies reported more than one risk factor for PPCS development following mTBIs that were generally the results of sports-related concussions and car accidents. The most prevalent risk factor associated with PPCS was the female sex. Social factors/personality traits, anxiety, mental health disorders, or other health conditions from their past medical history, the occurrence of headache/migraines during TBI recovery, somatization, physical activity, and litigation were also reported to contribute to PPCS risk. An exhaustive approach is required to mitigate the risk of PPCS and to ensure optimal recovery after concussive events. However, larger prospective cohort studies evaluating patients that were examined and treated with standardized protocols could be needed to further validate these associations and mandate the highest risk factors for delayed recovery.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

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-1ß 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.

A review of the personality traits in post-concussion syndrome.

INTRODUCTION: Various manifestations ranging from physical symptoms to cognitive and emotional impairments could often be seen following head concussions that lead to mild traumatic brain injury (mTBI). These symptoms are commonly comprising the post-concussion syndrome (PCS) and their resolution could be influenced by multiple factors. Personality traits have been suggested as potential risk factors for the emergence and persistence of PCS. In this study, we aimed to investigate the possible predisposition to PCS given by certain personality traits. METHODS: Prospective cohort studies, observational studies, and cross-phenotype polygenic risk score analyses were selected from the main scientific databases (PubMed/Medline, Scopus, EMBASE, Web of Science) based on multiple-step screening, using keywords (such as "personality traits", "post-concussion syndrome", "traumatic brain injury", "anxiety", "depression", "resilience", and "somatization") and inclusion/exclusion criteria (English written studies available in full text presenting relevant data on TBI patients and their personality traits; reviews, animal studies, and studies not written in English, not available in full text, or not presenting full demographical and clinical data were excluded). The investigated personality traits included emotional reserve, somatic trait anxiety, embitterment, mistrust, parental anxiety, state anxiety, trait anxiety, anxiety sensitivity, pain catastrophizing, helplessness, sports-concussion symptom load, and cognitive resilience. RESULTS: The reviewed data from 16 selected studies suggested that personality traits play an essential role in the development and persistence of PCS. Emotional reserve, cognitive resilience, and lower levels of somatic trait anxiety were associated with better outcomes in PCS. However, higher levels of anxiety sensitivity, pain catastrophizing, helplessness, and sports-concussion symptom load were associated with worse outcomes in PCS. Parental anxiety was not associated with persistent symptoms in children following concussion. Despite the statistical analysis regarding the included publications bias was low, further studies should further investigate the correlation between TBI and some personality traits, as some of the selected studies did not included healthy individuals and their psychological profiles for comparison and correlation analysis. CONCLUSION: Personality traits may help predict the development and persistence of PCS following mTBI. Understanding the personality traits roles in PCS could assist the development of targeted interventions for the prevention and treatment of PCS. Further research is needed to better understand the complex interactions between personality traits, neurobiological factors, and psychosocial factors in PCS.

Current Aspects on the Plastic Nano- and Microparticles Toxicity in Zebrafish-Focus on the Correlation between Oxidative Stress Responses and Neurodevelopment.

Recent reports focusing on the extent of plastic pollution have shown that many types of fibers and polymers can now be found in most marine species. The severe contamination of plastic nano-/microparticles (NPs/MPs) mainly results in immediate negative outcomes, such as organic impairments and tissue damage, as well as long-termed negative effects, such as developmental retardation and defects, chronic inflammation, oxidative stress (OS), metabolic imbalance, mutagenesis, and teratogenesis. Oxidative responses are currently considered the first line molecular signal to potential toxic stimuli exposure, as the oxidative balance in electron exchange and reactive oxygen species signaling provides efficient harmful stimuli processing. Abnormal signaling or dysregulated ROS metabolism-OS-could be an important source of cellular toxicity, the source of a vicious cycle of environmental and oxidative signaling-derived toxicity. As chemical environmental pollutants, plastic NPs/MPs can also be a cause of such toxicity. Thus, we aimed to correlate the possible toxic effects of plastic NPs/MPs in zebrafish models, by focusing on OS and developmental processes. We found that plastic NPs/MPs toxic effects could be observed during the entire developmental span of zebrafish in close correlation with OS-related changes. Excessive ROS production and decreased antioxidant enzymatic defense due to plastic NPs/MPs exposure and accumulation were frequently associated with acetylcholinesterase activity inhibition, suggesting important neurodevelopmental negative outcomes (cognitive abnormalities, neurodevelopmental retardation, behavioral impairments) and extraneuronal effects, such as impaired digestive physiology.

The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury.

(1) Background: In this study, we aimed to explore the regulatory mechanism of miR-124-3p microglial exosomes, as they were previously reported to modulate neuroinflammation and promote neuronal repair following traumatic brain injury (TBI). (2) Methods: Studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. (3) Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. Anti-inflammatory M2 polarization of microglia, mTOR signaling suppression, and BMVECs-mediated autophagy were reported as the main processes contributing to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. (4) Conclusions: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease-Oxidative Stress and Inflammation Relevance.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.

The Impact of Some Modulators of the Renin-Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model.

As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.

Metacognition in Schizophrenia Spectrum Disorders-Current Methods and Approaches.

Metacognition essentially represents "thinking about thinking", or the individual's capacity to control and monitor their own cognitive processes. Metacognition impairment in schizophrenia represents a core feature of the disease, and, in the last fifteen years, the subject has evolved into a growing study area concentrating on a wide variety of processes, such as clinical insight, autobiographical memory, cognitive beliefs, reasoning, and memory biases. Since metacognition is a complex subject, we wanted to focus on the different nuances of metacognition transposed into the lives of patients diagnosed with either schizophrenia or a schizoaffective disorder. Therefore, this narrative review aims to analyze the literature in order to provide an insight regarding the current methods and approaches in the study of metacognition in schizophrenia or schizoaffective disorders, as well as the results provided. Results from the reviewed studies showed that patients with schizophrenia have a lower metacognitive ability, which is strongly reflected in their lives. Studies to date have highlighted the interaction between schizophrenia symptoms and metacognition, which shows how metacognition impacts work performance, autobiographical memory, motivation, the severity of symptoms, and social cognition.

Functional Overlay Model of Persistent Post-Concussion Syndrome.

Persistent post-concussion syndrome (PPCS) is a complex and debilitating condition that can develop after head concussions or mild traumatic brain injury (mTBI). PPCS is characterized by a wide range of symptoms, including headaches, dizziness, fatigue, cognitive deficits, and emotional changes, that can persist for months or even years after the initial injury. Despite extensive research, the underlying mechanisms of PPCS are still poorly understood; furthermore, there are limited resources to predict PPCS development in mTBI patients and no established treatment. Similar to PPCS, the etiology and pathogenesis of functional neurological disorders (FNDs) are not clear neither fully described. Nonspecific multifactorial interactions that were also seen in PPCS have been identified as possible predispositions for FND onset and progression. Thus, we aimed to describe a functional overlay model of PPCS that emphasizes the interplay between functional and structural factors in the development and perpetuation of PPCS symptoms. Our model suggests that the initial brain injury triggers a cascade of physiological and psychological processes that disrupt the normal functioning of the brain leading to persistent symptoms. This disruption can be compounded by pre-existing factors, such as genetics, prior injury, and psychological distress, which can increase the vulnerability to PPCS. Moreover, specific interventions, such as cognitive behavioral therapy, neurofeedback, and physical exercise can target the PPCS treatment approach. Thus, the functional overlay model of PPCS provides a new framework for understanding the complex nature of this condition and for developing more effective treatments. By identifying and targeting specific functional factors that contribute to PPCS symptoms, clinicians and researchers can improve the diagnosis, management, and ultimately, outcomes of patients with this condition.

Post-Traumatic Headache: A Review of Prevalence, Clinical Features, Risk Factors, and Treatment Strategies.

Post-traumatic headache (PTH) is a common and debilitating consequence of mild traumatic brain injury (mTBI) that can occur over one year after the head impact event. Thus, better understanding of the underlying pathophysiology and risk factors could facilitate early identification and management of PTH. There are several factors that could influence the reporting of PTH prevalence, including the definition of concussion and PTH. The main risk factors for PTHs include a history of migraines or headaches, female gender, younger age, greater severity of the head injury, and co-occurring psychological symptoms, such as anxiety and depression. PTH clinical profiles vary based on onset, duration, and severity: tension-type headache, migraine headaches, cervicogenic headache, occipital neuralgia, and new daily persistent headache. Pharmacological treatments often consist of analgesics and non-steroidal anti-inflammatory drugs, tricyclic antidepressants, or antiepileptic medication. Cognitive behavioral therapy, relaxation techniques, biofeedback, and physical therapy could also be used for PTH treatment. Our work highlighted the need for more rigorous studies to better describe the importance of identifying risk factors and patient-centered treatments and to evaluate the effectiveness of the existing treatment options. Clinicians should consider a multidisciplinary approach to managing PTH, including pharmacotherapy, cognitive behavioral therapy, and lifestyle changes.

A Review of the Most Recent Clinical and Neuropathological Criteria for Chronic Traumatic Encephalopathy.

(1) Background: Chronic traumatic encephalopathy (CTE) is a complex pathological condition characterized by neurodegeneration, as a result of repeated head traumas. Currently, the diagnosis of CTE can only be assumed postmortem. Thus, the clinical manifestations associated with CTE are referred to as traumatic encephalopathy syndrome (TES), for which diagnostic multiple sets of criteria can be used. (2) Objectives: In this study, we aimed to present and discuss the limitations of the clinical and neuropathological diagnostic criteria for TES/CTE and to suggest a diagnostic algorithm enabling a more accurate diagnostic procedure. (3) Results: The most common diagnostic criteria for TES/CTE discriminate between possible, probable, and improbable. However, several key variations between the available diagnostic criteria suggest that the diagnosis of CTE can still only be given with postmortem neurophysiological examination. Thus, a TES/CTE diagnosis during life imposes a different level of certainty. Here, we are proposing a comprehensive algorithm of diagnosis criteria for TES/CTE based on the similarities and differences between the previous criteria. (4) Conclusions: The diagnosis of TES/CTE requires a multidisciplinary approach; thorough investigation for other neurodegenerative disorders, systemic illnesses, and/or psychiatric conditions that can account for the symptoms; and also complex investigations of patient history, psychiatric assessment, and blood and cerebrospinal fluid biomarker evaluation.

Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury and Post-Concussion Syndrome.

(1) Background: While mild traumatic brain injuries (TBIs) are a major public health issue, post-concussion syndrome (PCS) remains a controversial entity. In both cases, the clinical diagnosis is mainly based on the symptoms and brain imaging evaluation. The current molecular biomarkers were described from blood and cerebrospinal fluid (CSF), yet both fluid collection methods are invasive. Saliva could be preferred in molecular diagnosis due to its non-invasive and non-expensive methods of acquisition, transport, and samples processing. (2) Objectives: In the present study, we aimed to review the latest developments in salivary biomarkers and their potential role in diagnosing mild TBIs, and PCS. (3) Results: In TBIs and PCS, a few novel studies focusing on salivary biomarkers have emphasized their importance in diagnosis. The previous studies mainly focused on micro RNAs, and only a few on extracellular vesicles, neurofilament light chain, and S100B. (4) Conclusions: The combination between salivary biomarkers, clinical history and examination, self-reported symptoms, and cognitive/balance testing can provide a non-invasive alternative diagnostic methodology, as compared to the currently approved plasma and cerebrospinal fluid biomarkers.

The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options.

Ischemic strokes occur when the blood supply to a part of the brain is interrupted or reduced due to arterial blockage, and it often leads to damage to brain cells or death. According to a myriad of experimental studies, oxidative stress is an important pathophysiological mechanism of ischemic stroke. In this narrative review, we aimed to identify how the alterations of oxidative stress biomarkers could suggest a severity-reflecting diagnosis of ischemic stroke and how these interactions may provide new molecular targets for neuroprotective therapies. We performed an eligibility criteria-based search on three main scientific databases. We found that patients with acute ischemic stroke are characterized by increased oxidative stress markers levels, such as the total antioxidant capacity, F2-isoprostanes, hydroxynonenal, total and perchloric acid oxygen radical absorbance capacity (ORACTOT and ORACPCA), malondialdehyde (MDA), myeloperoxidase, and urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine. Thus, acute ischemic stroke is causing significant oxidative stress and associated molecular and cellular damage. The assessment of these molecular markers could be useful in diagnosing ischemic stroke, finding its causes, predicting its severity and outcomes, reducing its impact on the cellular structures of the brain, and guiding preventive treatment towards antioxidant-based therapy as novel therapeutic alternatives.

The Quest for Neurodegenerative Disease Treatment-Focusing on Alzheimer's Disease Personalised Diets.

Dementia represents a clinical syndrome characterised by progressive decline in memory, language, visuospatial and executive function, personality, and behaviour, causing loss of abilities to perform instrumental or essential activities of daily living. The most common cause of dementia is Alzheimer's disease (AD), which accounts for up to 80% of all dementia cases. Despite that extensive studies regarding the etiology and risk factors have been performed in recent decades, and how the current knowledge about AD pathophysiology significantly improved with the recent advances in science and technology, little is still known about its treatment options. In this controverted context, a nutritional approach could be a promising way to formulate improved AD management strategies and to further analyse possible treatment strategy options based on personalised diets, as Nutritional Psychiatry is currently gaining relevance in neuropsychiatric disease treatment. Based on the current knowledge of AD pathophysiology, as well as based on the repeatedly documented anti-inflammatory and antioxidant potential of different functional foods, we aimed to find, describe, and correlate several dietary compounds that could be useful in formulating a nutritional approach in AD management. We performed a screening for relevant studies on the main scientific databases using keywords such as "Alzheimer's disease", "dementia", "treatment", "medication", "treatment alternatives", "vitamin E", "nutrition", "selenium", "Ginkgo biloba", "antioxidants", "medicinal plants", and "traditional medicine" in combinations. Results: nutrients could be a key component in the physiologic and anatomic development of the brain. Several nutrients have been studied in the pursuit of the mechanism triggered by the pathology of AD: vitamin D, fatty acids, selenium, as well as neuroprotective plant extracts (i.e., Ginkgo biloba, Panax ginseng, Curcuma longa), suggesting that the nutritional patterns could modulate the cognitive status and provide neuroprotection. The multifactorial origin of AD development and progression could suggest that nutrition could greatly contribute to the complex pathological picture. The identification of adequate nutritional interventions and the not yet fully understood nutrient activity in AD could be the next steps in finding several innovative treatment options for neurodegenerative disorders.

Exploring the Potential of Exosomal Biomarkers in Mild Traumatic Brain Injury and Post-Concussion Syndrome: A Systematic Review.

BACKGROUND: Alongside their long-term effects, post-concussion syndrome (PCS) and mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. In this study, we aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS. METHODS: A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic. RESULTS: The analyzed studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aß), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS as well as repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS. CONCLUSION: Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains.

Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

A Mini-Review Regarding the Modalities to Study Neurodevelopmental Disorders-Like Impairments in Zebrafish-Focussing on Neurobehavioural and Psychological Responses.

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-hatching embryo stage, such as memory, perception, affective-like, and social behaviors can be relevant in ASD and schizophrenia research. The neurophysiological processes impaired in both ASD and schizophrenia are generally highly conserved across all vertebrates. However, the relatively late individual development and conscious social behavior exhibited later in the larval stage are some of the most important limitations of these model animal species.