DOI: https://doi.org/10.37349/en.2022.00001
The gut microbiota and dysbiosis have been implicated in various metabolic diseases and gastrointestinal disorders. Recently, there has been growing evidence suggesting the influence of gut microbiota on neurological disorders, including autism. Although the number of children diagnosed with autism is increasing, the exact cause of the disease remains unknown. Numerous factors, such as genetics, environment, and diet, appear to contribute to its onset. Nevertheless, a degree of general consensus exists regarding the notion that the disease’s progression likely demands the participation of multiple factors. Among the potential causes, the role of the microbiota is particularly intriguing. The gut and brain have extensive connections, with a significant number of neuronal cells in the gut, and autism is often associated with gastrointestinal issues. In this review, the most recent information available on autism and microbiota has been analyzed. Findings of this study indicate that: (1) the microbiota is clearly altered in individuals with autism spectrum disorder (ASD); (2) microbiota transplantation appears to be effective in reducing the severity of autism symptoms; (3) while the microbiota is not solely responsible for the onset of autism, it likely plays a significant role. Considering all the available information, it is suggested that modifying the gut microbiota may have a positive impact on individuals with autism. This opens up possibilities for the use of pre- or probiotics in the treatment of children with ASD, as well as the potential use of fecal microbiota transfer.
The gut microbiota and dysbiosis have been implicated in various metabolic diseases and gastrointestinal disorders. Recently, there has been growing evidence suggesting the influence of gut microbiota on neurological disorders, including autism. Although the number of children diagnosed with autism is increasing, the exact cause of the disease remains unknown. Numerous factors, such as genetics, environment, and diet, appear to contribute to its onset. Nevertheless, a degree of general consensus exists regarding the notion that the disease’s progression likely demands the participation of multiple factors. Among the potential causes, the role of the microbiota is particularly intriguing. The gut and brain have extensive connections, with a significant number of neuronal cells in the gut, and autism is often associated with gastrointestinal issues. In this review, the most recent information available on autism and microbiota has been analyzed. Findings of this study indicate that: (1) the microbiota is clearly altered in individuals with autism spectrum disorder (ASD); (2) microbiota transplantation appears to be effective in reducing the severity of autism symptoms; (3) while the microbiota is not solely responsible for the onset of autism, it likely plays a significant role. Considering all the available information, it is suggested that modifying the gut microbiota may have a positive impact on individuals with autism. This opens up possibilities for the use of pre- or probiotics in the treatment of children with ASD, as well as the potential use of fecal microbiota transfer.
DOI: https://doi.org/10.37349/en.2023.00018
Several bare metals, self-expanding stents have been approved by the Food and Drug Administration (FDA) to treat carotid stenosis, but no covered stents have been particularly examined or approved for carotid or cerebrovascular applications. Nonetheless, there are a number of potentially useful applications for covered stents in the brachiocephalic, carotid, and even intracranial arteries. As with currently accepted applications for bare metal carotid stents, the use of covered stents in carotid arteries has been reserved for patients who are at high risk for complications with open surgical management of their specific problem. The present case report emphasizes the safety and efficacy of covered stent in complex carotid artery reconstruction entailing stenosis and aneurysmal dilatation and through light on its impact on minimizing the risk of ischemic complications associated with endovascular or surgical carotid sacrifice.
Several bare metals, self-expanding stents have been approved by the Food and Drug Administration (FDA) to treat carotid stenosis, but no covered stents have been particularly examined or approved for carotid or cerebrovascular applications. Nonetheless, there are a number of potentially useful applications for covered stents in the brachiocephalic, carotid, and even intracranial arteries. As with currently accepted applications for bare metal carotid stents, the use of covered stents in carotid arteries has been reserved for patients who are at high risk for complications with open surgical management of their specific problem. The present case report emphasizes the safety and efficacy of covered stent in complex carotid artery reconstruction entailing stenosis and aneurysmal dilatation and through light on its impact on minimizing the risk of ischemic complications associated with endovascular or surgical carotid sacrifice.
DOI: https://doi.org/10.37349/en.2023.00019
Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided.
Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided.
DOI: https://doi.org/10.37349/en.2023.00020
This article belongs to the special issue Novel Therapeutic Approaches for the Treatment of Depression
Brain development, a complex process, consisting of several phases, starting as early as two weeks after conception, and continuing through childhood till early adolescence, is crucial for the development of properly functioning body systems, behavioral traits, and neurocognitive abilities. Infancy and childhood are recognized as important periods for initial brain formation, however in later stages of life, such as childhood and adulthood, experiences, together with environmental exposures, can still influence brain physiology. The developing brain is particularly susceptible to epigenetic changes with many factors being proposed as modifiers by directly impacting DNA methylation as well as histone and chromatin modifications within genes implicated in development. These factors include: maternal stress and diet, exposure to pollutants, sleep quality, as well as dietary habits. Evidence indicates exposures to environmental threats can lead to inappropriate neurological, metabolic, and endocrine functioning often mediated by epigenetic mechanisms with symptoms manifesting themselves as early as childhood or in later stages of life. Therefore, the main aim of this review is to evaluate the current studies focused on negative environmental exposures and their consequences on the developing brain directed by epigenetic mechanisms.
Brain development, a complex process, consisting of several phases, starting as early as two weeks after conception, and continuing through childhood till early adolescence, is crucial for the development of properly functioning body systems, behavioral traits, and neurocognitive abilities. Infancy and childhood are recognized as important periods for initial brain formation, however in later stages of life, such as childhood and adulthood, experiences, together with environmental exposures, can still influence brain physiology. The developing brain is particularly susceptible to epigenetic changes with many factors being proposed as modifiers by directly impacting DNA methylation as well as histone and chromatin modifications within genes implicated in development. These factors include: maternal stress and diet, exposure to pollutants, sleep quality, as well as dietary habits. Evidence indicates exposures to environmental threats can lead to inappropriate neurological, metabolic, and endocrine functioning often mediated by epigenetic mechanisms with symptoms manifesting themselves as early as childhood or in later stages of life. Therefore, the main aim of this review is to evaluate the current studies focused on negative environmental exposures and their consequences on the developing brain directed by epigenetic mechanisms.
DOI: https://doi.org/10.37349/en.2023.00021
Life is the highest form of adaptation to the environment which is based on energy metabolism. To maintain life, the neuromuscular system must constantly interact with the environment. The striatal muscles are the main energy consumer and their access to energy fuel is mainly limited by the brain’s needs. In the state of wakefulness, the brain must continuously process streams of sensory signals and respond to them with motor actions. At the same time, the brain to be efficient must memorize the sensory-movement relationships. Brain memory networking requires additional energy allocation, and due to limited systemic energy resources, the processes of memorization are completed during the sleep phase when the inactive muscular system allows allocating the energy fuel to the brain functions such as memory trace formation and the removal of the activity-dependent waste products. Both physiological processes can be completed during sleep only, and consequently, chronic sleep disorder leads to pathological changes in brain functioning and escalation of neurodegenerative processes. Consequently, sleep disorders become the main cause of dementia which is the prodrome of Alzheimer’s disease.
Life is the highest form of adaptation to the environment which is based on energy metabolism. To maintain life, the neuromuscular system must constantly interact with the environment. The striatal muscles are the main energy consumer and their access to energy fuel is mainly limited by the brain’s needs. In the state of wakefulness, the brain must continuously process streams of sensory signals and respond to them with motor actions. At the same time, the brain to be efficient must memorize the sensory-movement relationships. Brain memory networking requires additional energy allocation, and due to limited systemic energy resources, the processes of memorization are completed during the sleep phase when the inactive muscular system allows allocating the energy fuel to the brain functions such as memory trace formation and the removal of the activity-dependent waste products. Both physiological processes can be completed during sleep only, and consequently, chronic sleep disorder leads to pathological changes in brain functioning and escalation of neurodegenerative processes. Consequently, sleep disorders become the main cause of dementia which is the prodrome of Alzheimer’s disease.
DOI: https://doi.org/10.37349/en.2023.00022
This article belongs to the special issue Alzheimer’s Disease
As the average lifespan has increased, memory disorders have become a more pressing public health concern. However, dementia in the elderly population is often neglected in light of other health priorities. Therefore, expanding the knowledge surrounding the pathology of dementia will allow more informed decision-making regarding treatment within elderly and older adult populations. An important emerging avenue in dementia research is understanding the vascular contributors to dementia. This review summarizes potential causes of vascular cognitive impairment like stroke, microinfarction, hypertension, atherosclerosis, blood-brain barrier dysfunction, and cerebral amyloid angiopathy. Also, this review address treatments that target these vascular impairments that also show promising results in reducing patient’s risk for and experience of dementia.
As the average lifespan has increased, memory disorders have become a more pressing public health concern. However, dementia in the elderly population is often neglected in light of other health priorities. Therefore, expanding the knowledge surrounding the pathology of dementia will allow more informed decision-making regarding treatment within elderly and older adult populations. An important emerging avenue in dementia research is understanding the vascular contributors to dementia. This review summarizes potential causes of vascular cognitive impairment like stroke, microinfarction, hypertension, atherosclerosis, blood-brain barrier dysfunction, and cerebral amyloid angiopathy. Also, this review address treatments that target these vascular impairments that also show promising results in reducing patient’s risk for and experience of dementia.
DOI: https://doi.org/10.37349/en.2023.00023
Aim:
Apolipoprotein E (ApoE) isoforms, especially the ApoE4 isoform, are genetic risk factors for Alzheimer’s disease (AD). Moreover, the APOE ε4 haplotype has a dose-dependent association with an increased risk of amyloid-related imaging abnormalities (ARIA) in individuals receiving disease-modifying therapy for AD. Therefore, the importance of APOE genotyping or proteotyping has been highlighted. Here, the authors developed fully automated chemiluminescence enzyme-immunoassay kit for ApoE4 and Pan-ApoE, and evaluated their diagnostic concordance with the APOE genotyping.
Methods:
One hundred seventy-eight specimens were analyzed using the Lumipulse® G ApoE4 and Pan-ApoE for the ApoE proteotype and evaluated its diagnostic concordance with the APOE genotype.
Results:
The ApoE4 kit specifically detected the ApoE4 concentration in plasma samples, and the polymorphism could be classified clearly by the ratio of ApoE4 and Pan-ApoE amount in plasma.
Conclusions:
The combination of Pan-ApoE and ApoE4-specific chemiluminescent enzyme immunoassay (CLEIA) assay is useful for predicting APOE ε4 allele status.
Aim:
Apolipoprotein E (ApoE) isoforms, especially the ApoE4 isoform, are genetic risk factors for Alzheimer’s disease (AD). Moreover, the APOE ε4 haplotype has a dose-dependent association with an increased risk of amyloid-related imaging abnormalities (ARIA) in individuals receiving disease-modifying therapy for AD. Therefore, the importance of APOE genotyping or proteotyping has been highlighted. Here, the authors developed fully automated chemiluminescence enzyme-immunoassay kit for ApoE4 and Pan-ApoE, and evaluated their diagnostic concordance with the APOE genotyping.
Methods:
One hundred seventy-eight specimens were analyzed using the Lumipulse® G ApoE4 and Pan-ApoE for the ApoE proteotype and evaluated its diagnostic concordance with the APOE genotype.
Results:
The ApoE4 kit specifically detected the ApoE4 concentration in plasma samples, and the polymorphism could be classified clearly by the ratio of ApoE4 and Pan-ApoE amount in plasma.
Conclusions:
The combination of Pan-ApoE and ApoE4-specific chemiluminescent enzyme immunoassay (CLEIA) assay is useful for predicting APOE ε4 allele status.
DOI: https://doi.org/10.37349/en.2023.00024
This article belongs to the special issue Alzheimer’s Disease
The two mainstays of therapy for refractory epilepsy are medication and surgery. Child behavioral and cognitive aspects of epilepsy can be improved by using a specialized dietary regimen such as the ketogenic diet (KD). The purpose of this review is to expand our understanding of KD as a nutritional therapy for children with refractory epilepsy and to provide insight into the physiological aspects of its efficacy as an alternative to anti-seizure medication. Either directly or indirectly, ketones, glucose restriction, and polyunsaturated fatty acids regulate epileptic seizures. For KD to be effective, all three of these components must be present, even though the exact mechanism is unknown. Increasing gamma-aminobutyric acid, mitochondrial biogenesis, and oxidative phosphorylation levels can also serve as a means of promoting stable synaptic function while also decreasing neural activity and excitability. Most side effects of KD are caused by mild metabolic abnormalities such as acidosis, hyperuricemia, hypercholesterolemia, hypocalcemia, and hypomagnesemia. Since medium-chain triglycerides (MCTs) produce more ketones per calorie than long-chain triglycerides, individuals who consume MCTs can consume more carbohydrates and protein. This review demonstrated that KD therapy led to positive outcomes for patients with refractory epilepsy. Further study is needed to evaluate whether less restrictive and easier-to-follow diets, such as the modified Atkins diet and MCT diets, have a similar effect on seizure treatment as the standard KD.
The two mainstays of therapy for refractory epilepsy are medication and surgery. Child behavioral and cognitive aspects of epilepsy can be improved by using a specialized dietary regimen such as the ketogenic diet (KD). The purpose of this review is to expand our understanding of KD as a nutritional therapy for children with refractory epilepsy and to provide insight into the physiological aspects of its efficacy as an alternative to anti-seizure medication. Either directly or indirectly, ketones, glucose restriction, and polyunsaturated fatty acids regulate epileptic seizures. For KD to be effective, all three of these components must be present, even though the exact mechanism is unknown. Increasing gamma-aminobutyric acid, mitochondrial biogenesis, and oxidative phosphorylation levels can also serve as a means of promoting stable synaptic function while also decreasing neural activity and excitability. Most side effects of KD are caused by mild metabolic abnormalities such as acidosis, hyperuricemia, hypercholesterolemia, hypocalcemia, and hypomagnesemia. Since medium-chain triglycerides (MCTs) produce more ketones per calorie than long-chain triglycerides, individuals who consume MCTs can consume more carbohydrates and protein. This review demonstrated that KD therapy led to positive outcomes for patients with refractory epilepsy. Further study is needed to evaluate whether less restrictive and easier-to-follow diets, such as the modified Atkins diet and MCT diets, have a similar effect on seizure treatment as the standard KD.
DOI: https://doi.org/10.37349/en.2023.00025
This article belongs to the special issue Epilepsy
Epilepsy, a prevalent neurological disorder, is characterized by chronic seizures resulting from abnormal electrical activity in the brain. Adequate medical treatment allows roughly 70% of patients to enjoy a seizure-free life. However, throughout history, epilepsy has acquired diverse interpretations due to the experienced seizures, transforming the condition from a clinical issue into a social stigma. Therefore, the aim of this review study is to review stigma and psychosocial problems in patients with epilepsy (PwE). For this reason, this study utilises sources from the last ten years and reports current data. As a result of the review, it was found that societal discrimination in PwE arises primarily from inadequate knowledge, misconceptions, and negative attitudes toward the condition. Other contributing factors were include patients’ lower levels of education and income, frequent seizures due to inadequate treatment, age at onset, duration of the disease, depressive symptoms, and lack of social support. Also, it was found that the stigma individuals with epilepsy face plays a pivotal role in exacerbating their psychosocial problems. Unfortunately, stigma and psychosocial challenges appear to be in a vicious circle, with an increase in one increasing the other. Stigmatized patients tended to isolate themselves from society, further increasing their likelihood of experiencing a depressive mood or psychiatric comorbidity. Consequently, individuals with epilepsy encounter difficulties in various domains such as marriage, work, education, and personal life. Considering these significant psychosocial burdens, it is essential to recognize that epilepsy surpasses its medical implications. Unfortunately, current efforts to reduce stigma remain insufficient, necessitating urgent and comprehensive measures to address this issue.
Epilepsy, a prevalent neurological disorder, is characterized by chronic seizures resulting from abnormal electrical activity in the brain. Adequate medical treatment allows roughly 70% of patients to enjoy a seizure-free life. However, throughout history, epilepsy has acquired diverse interpretations due to the experienced seizures, transforming the condition from a clinical issue into a social stigma. Therefore, the aim of this review study is to review stigma and psychosocial problems in patients with epilepsy (PwE). For this reason, this study utilises sources from the last ten years and reports current data. As a result of the review, it was found that societal discrimination in PwE arises primarily from inadequate knowledge, misconceptions, and negative attitudes toward the condition. Other contributing factors were include patients’ lower levels of education and income, frequent seizures due to inadequate treatment, age at onset, duration of the disease, depressive symptoms, and lack of social support. Also, it was found that the stigma individuals with epilepsy face plays a pivotal role in exacerbating their psychosocial problems. Unfortunately, stigma and psychosocial challenges appear to be in a vicious circle, with an increase in one increasing the other. Stigmatized patients tended to isolate themselves from society, further increasing their likelihood of experiencing a depressive mood or psychiatric comorbidity. Consequently, individuals with epilepsy encounter difficulties in various domains such as marriage, work, education, and personal life. Considering these significant psychosocial burdens, it is essential to recognize that epilepsy surpasses its medical implications. Unfortunately, current efforts to reduce stigma remain insufficient, necessitating urgent and comprehensive measures to address this issue.
DOI: https://doi.org/10.37349/en.2023.00026
This article belongs to the special issue Epilepsy
Aim:
One of the main risk factors for an ischemic stroke is significant carotid artery stenosis, and extracranial severe carotid artery stenosis accounts for 20% of ischemic strokes. Prior to the development of carotid artery stenting (CAS), the only effective and reliable treatment for carotid artery stenosis was carotid endarterectomy (CEA). This study compares the results of CAS and CEA in patients with significant carotid artery stenosis.
Methods:
Between 2018 and 2022, hospital records of all patients who underwent carotid artery revascularization at the institution were retrospectively analyzed. Patients were divided into two groups depending on whether CEA or CAS was performed for carotid revascularization. Propensity score matching was performed to reduce bias by equating the baseline clinical characteristics of the groups. To compare 30-day, 1-year, and long-term outcomes, rates of transient ischemic attack (TIA), myocardial infarction, stroke, all-cause mortality, and composite endpoints were analyzed.
Results:
After PSM, 76 patients each in the CEA and CAS groups were compared. The mean age was 69.80 years ± 11.35 years and 121 (80%) were male. The patients were followed up for a mean of 33 months ± 6 months. The incidence of TIA in the perioperative period [9 (12%) vs. 4 (5%); P < 0.05], TIA and composite endpoint at 1-year period [11 (15%) vs. 2 (3%); P < 0.05 and 27 (36%) vs. 16 (21%); P < 0.05, respectively] were significantly higher in the CAS group than in the CEA group. No difference was observed between the groups in the long-term.
Conclusions:
There was no noticeable difference between the CEA and CAS groups in the examination of cases with severe carotid artery stenosis in terms of 1-month, and 1-year results (apart from TIA and composite endpoints), or long-term outcomes. Extracranial carotid artery stenosis can be treated safely and effectively also by CAS.
Aim:
One of the main risk factors for an ischemic stroke is significant carotid artery stenosis, and extracranial severe carotid artery stenosis accounts for 20% of ischemic strokes. Prior to the development of carotid artery stenting (CAS), the only effective and reliable treatment for carotid artery stenosis was carotid endarterectomy (CEA). This study compares the results of CAS and CEA in patients with significant carotid artery stenosis.
Methods:
Between 2018 and 2022, hospital records of all patients who underwent carotid artery revascularization at the institution were retrospectively analyzed. Patients were divided into two groups depending on whether CEA or CAS was performed for carotid revascularization. Propensity score matching was performed to reduce bias by equating the baseline clinical characteristics of the groups. To compare 30-day, 1-year, and long-term outcomes, rates of transient ischemic attack (TIA), myocardial infarction, stroke, all-cause mortality, and composite endpoints were analyzed.
Results:
After PSM, 76 patients each in the CEA and CAS groups were compared. The mean age was 69.80 years ± 11.35 years and 121 (80%) were male. The patients were followed up for a mean of 33 months ± 6 months. The incidence of TIA in the perioperative period [9 (12%) vs. 4 (5%); P < 0.05], TIA and composite endpoint at 1-year period [11 (15%) vs. 2 (3%); P < 0.05 and 27 (36%) vs. 16 (21%); P < 0.05, respectively] were significantly higher in the CAS group than in the CEA group. No difference was observed between the groups in the long-term.
Conclusions:
There was no noticeable difference between the CEA and CAS groups in the examination of cases with severe carotid artery stenosis in terms of 1-month, and 1-year results (apart from TIA and composite endpoints), or long-term outcomes. Extracranial carotid artery stenosis can be treated safely and effectively also by CAS.
DOI: https://doi.org/10.37349/en.2023.00027
Neuropathic pain is an increasingly common disease affecting millions of individuals worldwide. Refractory pain poses a significant impact on patients’ quality of life, financial and economic stability, and social interaction. Numerous effective modalities for treatment of refractory neuropathic pain are presently available. Currently, many options provide symptomatic treatment but are associated with an unfavorable side effect profile and increased risk of addiction. The present investigation reviews current medical management for refractory neuropathic pain including the use of antidepressants, anticonvulsants, gabapentinoids and opioid therapy, as well as interventional pain procedures such as spinal cord stimulation (SCS) and intrathecal targeted drug delivery. While multidisciplinary management with lifestyle modification and pharmacologic regimens remains at the forefront of treating many of these patients, interventional modalities are growing in popularity and have been demonstrated to be highly efficacious. In this regard, continued understanding of the pathophysiology surrounding refractory neuropathic pain has led to the development of interventional procedures and better outcomes for patients suffering from refractory neuropathic pain. When and if patients fail conservative therapy, interventional techniques are desirable alternatives for pain management. SCS and intrathecal targeted drug delivery are important tools for the treatment of refractory neuropathic pain. In summary, treatment modalities for refractory neuropathic pain are evolving with demonstrated efficacy. This review aims to outline the efficacy of various interventional procedures for refractory neuropathic pain in comparison to traditional drug therapies.
Neuropathic pain is an increasingly common disease affecting millions of individuals worldwide. Refractory pain poses a significant impact on patients’ quality of life, financial and economic stability, and social interaction. Numerous effective modalities for treatment of refractory neuropathic pain are presently available. Currently, many options provide symptomatic treatment but are associated with an unfavorable side effect profile and increased risk of addiction. The present investigation reviews current medical management for refractory neuropathic pain including the use of antidepressants, anticonvulsants, gabapentinoids and opioid therapy, as well as interventional pain procedures such as spinal cord stimulation (SCS) and intrathecal targeted drug delivery. While multidisciplinary management with lifestyle modification and pharmacologic regimens remains at the forefront of treating many of these patients, interventional modalities are growing in popularity and have been demonstrated to be highly efficacious. In this regard, continued understanding of the pathophysiology surrounding refractory neuropathic pain has led to the development of interventional procedures and better outcomes for patients suffering from refractory neuropathic pain. When and if patients fail conservative therapy, interventional techniques are desirable alternatives for pain management. SCS and intrathecal targeted drug delivery are important tools for the treatment of refractory neuropathic pain. In summary, treatment modalities for refractory neuropathic pain are evolving with demonstrated efficacy. This review aims to outline the efficacy of various interventional procedures for refractory neuropathic pain in comparison to traditional drug therapies.
DOI: https://doi.org/10.37349/en.2023.00028
This article belongs to the special issue Neuropathic Pain
The circadian rhythm is a critical system that governs an organism’s functions in alignment with the light-dark cycle. Melatonin release from the pineal gland plays a crucial role in regulating the internal clock of the body. Multiple neurotransmitter systems in the central nervous system are linked to the release of melatonin. In this review, the relationship between circadian rhythm, melatonin secretion and various neurotransmitter systems are mainly discussed. Serotonin regulates the circadian rhythm through projections from raphe nuclei. Agomelatine is an example of the synergistic interaction between melatonin and serotonin. Melatonergic agents and selective serotonin reuptake inhibitors also exert notable impacts on depression in concomitant use. Dopamine has an inhibitory effect on melatonin release, while melatonin also inhibits dopamine release. This should be taken into account when considering the use of melatonin in Parkinson’s disease. On the contrary, use of melatonin may offer therapeutic advantages for schizophrenia and tardive dyskinesia. The interaction between norepinephrine and melatonin exhibits diurnal variability, with norepinephrine promoting arousal and inhibiting daytime melatonin secretion. Melatonergic neurons also exert a specific protective influence on cholinergic neurons. Interaction between the histaminergic and melatonergic systems is significant, particularly in association with immunity, sleep, and circadian rhythm. Novel ligands with dual-acting properties, interacting with both the histaminergic and melatonergic systems are investigated. Currently, there is a limited number of approved melatonergic agents that primarily demonstrate positive effects in addressing insomnia and depression. However, there is considerable potential in studying new agents that target both the melatonergic and other neurotransmitter systems, which alleviate various conditions, including neurodegenerative diseases, dementia, autoimmune diseases, allergic diseases, epilepsy, and other neuropsychiatric disorders. The ongoing process of developing and evaluating new ligands selectively targeting the melatonergic system remains crucial in understanding the complex relationship between these systems.
The circadian rhythm is a critical system that governs an organism’s functions in alignment with the light-dark cycle. Melatonin release from the pineal gland plays a crucial role in regulating the internal clock of the body. Multiple neurotransmitter systems in the central nervous system are linked to the release of melatonin. In this review, the relationship between circadian rhythm, melatonin secretion and various neurotransmitter systems are mainly discussed. Serotonin regulates the circadian rhythm through projections from raphe nuclei. Agomelatine is an example of the synergistic interaction between melatonin and serotonin. Melatonergic agents and selective serotonin reuptake inhibitors also exert notable impacts on depression in concomitant use. Dopamine has an inhibitory effect on melatonin release, while melatonin also inhibits dopamine release. This should be taken into account when considering the use of melatonin in Parkinson’s disease. On the contrary, use of melatonin may offer therapeutic advantages for schizophrenia and tardive dyskinesia. The interaction between norepinephrine and melatonin exhibits diurnal variability, with norepinephrine promoting arousal and inhibiting daytime melatonin secretion. Melatonergic neurons also exert a specific protective influence on cholinergic neurons. Interaction between the histaminergic and melatonergic systems is significant, particularly in association with immunity, sleep, and circadian rhythm. Novel ligands with dual-acting properties, interacting with both the histaminergic and melatonergic systems are investigated. Currently, there is a limited number of approved melatonergic agents that primarily demonstrate positive effects in addressing insomnia and depression. However, there is considerable potential in studying new agents that target both the melatonergic and other neurotransmitter systems, which alleviate various conditions, including neurodegenerative diseases, dementia, autoimmune diseases, allergic diseases, epilepsy, and other neuropsychiatric disorders. The ongoing process of developing and evaluating new ligands selectively targeting the melatonergic system remains crucial in understanding the complex relationship between these systems.
DOI: https://doi.org/10.37349/en.2023.00029
This article belongs to the special issue Circadian Rhythm and Melatonin
Neural disorders refer to conditions of the nervous system due to infection or degeneration of the neurons leading to either neurodegenerative disorder or neuropsychiatric disorder. Some such disorders of the nervous system include Parkinsons’s disease, depression, amnesia, dementia, Alzheimer’s disease, schizophrenia, cerebrovascular impairment, epilepsy, seizure disorders, etc. In conventional medical system, some medicines belonging to the class of psychodelic drugs, sedatives, neurotransmitters, neuro-stimulants, etc. are in extensive use. Unfortunately, most of these drugs either delay the progression of the neural disorder or leave the patient with prominent adverse side effects. Several potent bioactive compounds with neuroprotective potential have been reported from medicinal plants and some of them have been found to be highly effective. Belonging from natural sources, mostly, the plant derived compounds exhibit minimum or no cytotoxicity at a prescribed standardised dose against a particular health ailment. Many such phytocompounds from plant sources with potent neuroprotective activities have been in use in Ayurvedacharya, Unani, and Chinese medicine for ages. The compounds if isolated chemically, modified to make more potent neuroprotective derivatives and utilised to make highly effective neuroprotective pharmaceutical formulations with minimum side effects, may open new revolutionary doorways in neuropharmacology. In this review, it has been briefly discussed about the neuroprotective compounds isolated from certain indigenous plants of West Bengal, India, and their mechanism of action.
Neural disorders refer to conditions of the nervous system due to infection or degeneration of the neurons leading to either neurodegenerative disorder or neuropsychiatric disorder. Some such disorders of the nervous system include Parkinsons’s disease, depression, amnesia, dementia, Alzheimer’s disease, schizophrenia, cerebrovascular impairment, epilepsy, seizure disorders, etc. In conventional medical system, some medicines belonging to the class of psychodelic drugs, sedatives, neurotransmitters, neuro-stimulants, etc. are in extensive use. Unfortunately, most of these drugs either delay the progression of the neural disorder or leave the patient with prominent adverse side effects. Several potent bioactive compounds with neuroprotective potential have been reported from medicinal plants and some of them have been found to be highly effective. Belonging from natural sources, mostly, the plant derived compounds exhibit minimum or no cytotoxicity at a prescribed standardised dose against a particular health ailment. Many such phytocompounds from plant sources with potent neuroprotective activities have been in use in Ayurvedacharya, Unani, and Chinese medicine for ages. The compounds if isolated chemically, modified to make more potent neuroprotective derivatives and utilised to make highly effective neuroprotective pharmaceutical formulations with minimum side effects, may open new revolutionary doorways in neuropharmacology. In this review, it has been briefly discussed about the neuroprotective compounds isolated from certain indigenous plants of West Bengal, India, and their mechanism of action.
DOI: https://doi.org/10.37349/en.2023.00030
This article belongs to the special issue Medicinal Plants and Bioactive Phytochemicals in Neuroprotection
Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited von Hippel-Lindau disease or can appear sporadically. This review will investigate current and emerging treatments for cerebral tumors. It will focus on the current and, more importantly, developing hemangioblastoma treatments. Surgical resectioning and radiotherapy are effective treatment options for cerebral tumors, whereas chemotherapies are not commonly used due to their limited ability to penetrate the blood-brain barrier. Recent chemotherapies have shown promise, but further research is needed to determine the efficacy as a treatment for hemangioblastomas. New advances in brachytherapy and immunotherapy are considered promising treatment options for hemangioblastoma. This review aims to offer valuable insights into the latest developments in hemangioblastoma treatments.
Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited von Hippel-Lindau disease or can appear sporadically. This review will investigate current and emerging treatments for cerebral tumors. It will focus on the current and, more importantly, developing hemangioblastoma treatments. Surgical resectioning and radiotherapy are effective treatment options for cerebral tumors, whereas chemotherapies are not commonly used due to their limited ability to penetrate the blood-brain barrier. Recent chemotherapies have shown promise, but further research is needed to determine the efficacy as a treatment for hemangioblastomas. New advances in brachytherapy and immunotherapy are considered promising treatment options for hemangioblastoma. This review aims to offer valuable insights into the latest developments in hemangioblastoma treatments.
DOI: https://doi.org/10.37349/en.2023.00031
This article belongs to the special issue Cerebral Ischemia, Genetics, Comorbidities, Risk Factors and New Therapeutic Options for Neurorestoration
For more than a decade now, research studies, proof of concept work, and clinical trials have endeavored to understand how mesenchymal stem cells might be used to help protect, repair, and/or regenerate damaged brain tissue following stroke. To date, the majority of studies have not demonstrated significant improvements in either morbidity or medium-long-term outcome, although safety has been relatively well proven. Limitations are likely to be linked to the pathobiological complexity and seriousness of stroke tissue damage, low efficacy of treatment, and short half-life of bio-active proteins released by stem cells. This article will highlight the heterogeneity and limitation of completed studies and the current status of ongoing work. At the same time, the potential of other combinational type treatments, such as drug-loading and targeting, and the use of hydrogels is discussed.
For more than a decade now, research studies, proof of concept work, and clinical trials have endeavored to understand how mesenchymal stem cells might be used to help protect, repair, and/or regenerate damaged brain tissue following stroke. To date, the majority of studies have not demonstrated significant improvements in either morbidity or medium-long-term outcome, although safety has been relatively well proven. Limitations are likely to be linked to the pathobiological complexity and seriousness of stroke tissue damage, low efficacy of treatment, and short half-life of bio-active proteins released by stem cells. This article will highlight the heterogeneity and limitation of completed studies and the current status of ongoing work. At the same time, the potential of other combinational type treatments, such as drug-loading and targeting, and the use of hydrogels is discussed.
DOI: https://doi.org/10.37349/en.2023.00015
This article belongs to the special issue Neuroinflammation in the Ageing and the Injured Brain
Globally, the incidence of Parkinson’s disease (PD) is increasing faster than other neurodegenerative disorders. Neuropathologically, PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta due to the accumulation of aggregates of misfolded α-synuclein (α-Syn) in the cytoplasm of these neurons, forming Lewy bodies. Extracellular vesicles (EVs) are associated with the spread of α-Syn to different brain areas. However, at the same time that these EVs contribute to the pathophysiology of PD, they can also be explored as therapeutic, serving as a vehicle to deliver specific molecules, since these vesicles can easily cross the blood-brain barrier. Thus, this review summarizes the recent progress in EVs as a therapeutic strategy for PD, focusing on their delivery to the brain, and discusses the potential challenges and future directions in this field.
Globally, the incidence of Parkinson’s disease (PD) is increasing faster than other neurodegenerative disorders. Neuropathologically, PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta due to the accumulation of aggregates of misfolded α-synuclein (α-Syn) in the cytoplasm of these neurons, forming Lewy bodies. Extracellular vesicles (EVs) are associated with the spread of α-Syn to different brain areas. However, at the same time that these EVs contribute to the pathophysiology of PD, they can also be explored as therapeutic, serving as a vehicle to deliver specific molecules, since these vesicles can easily cross the blood-brain barrier. Thus, this review summarizes the recent progress in EVs as a therapeutic strategy for PD, focusing on their delivery to the brain, and discusses the potential challenges and future directions in this field.
DOI: https://doi.org/10.37349/en.2023.00016
This article belongs to the special issue Extracellular Vesicles as Cell-based Therapeutics
Earth’s rotation generates the basic circadian rhythm of day and night to which all living organisms must adapt to survive. In mammals, this happens thanks to a central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and to peripheral clock genes at the cellular level. The main environmental cue capable of synchronizing such clocks is light sensed by retinal ganglion cells signaling through a complex nervous pathway to the pineal gland which ultimately regulates melatonin synthesis that occurs during the night, darkness hours in all mammals. The central clock synchronized by melatonin drives the circadian oscillation of the sympathetic nervous system (SNS) adrenergic activity which in turn controls glucocorticoid production in the adrenal glands. These oscillations are integrated with peripheral cellular clocks by still not completely understood mechanisms and drive the homeostatic control of activity-rest (sleep) cycles, cardiovascular activity, body temperature, and immune-hematopoietic functions. The neuronal and hormonal mechanisms governing the circadian oscillation of hematopoiesis and immunity will be addressed in this review focusing on those offering therapeutic perspectives.
Earth’s rotation generates the basic circadian rhythm of day and night to which all living organisms must adapt to survive. In mammals, this happens thanks to a central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and to peripheral clock genes at the cellular level. The main environmental cue capable of synchronizing such clocks is light sensed by retinal ganglion cells signaling through a complex nervous pathway to the pineal gland which ultimately regulates melatonin synthesis that occurs during the night, darkness hours in all mammals. The central clock synchronized by melatonin drives the circadian oscillation of the sympathetic nervous system (SNS) adrenergic activity which in turn controls glucocorticoid production in the adrenal glands. These oscillations are integrated with peripheral cellular clocks by still not completely understood mechanisms and drive the homeostatic control of activity-rest (sleep) cycles, cardiovascular activity, body temperature, and immune-hematopoietic functions. The neuronal and hormonal mechanisms governing the circadian oscillation of hematopoiesis and immunity will be addressed in this review focusing on those offering therapeutic perspectives.
DOI: https://doi.org/10.37349/en.2023.00017
This article belongs to the special issue Circadian Rhythm and Melatonin
Stroke is a leading cause of morbidity and mortality. The advent of mechanical thrombectomy has largely improved patient outcomes. This article reviews the features and outcomes associated with aspiration, stent retrievers, and combination catheters used in current practice. There is also a discussion on clinical considerations based on anatomical features and clot composition. The reperfusion grading scale and outcome metrics commonly used following thrombectomy when a patient is still in the hospital are reviewed. Lastly, there are proposed discharge and outpatient follow-up goals in caring for patients hospitalized for a stroke.
Stroke is a leading cause of morbidity and mortality. The advent of mechanical thrombectomy has largely improved patient outcomes. This article reviews the features and outcomes associated with aspiration, stent retrievers, and combination catheters used in current practice. There is also a discussion on clinical considerations based on anatomical features and clot composition. The reperfusion grading scale and outcome metrics commonly used following thrombectomy when a patient is still in the hospital are reviewed. Lastly, there are proposed discharge and outpatient follow-up goals in caring for patients hospitalized for a stroke.
DOI: https://doi.org/10.37349/en.2022.00007
Exposure to stressful conditions plays a critical role in brain processes, including neural plasticity, synaptic transmission, and cognitive functions. Since memory-related brain regions, the hippocampus (Hip), the amygdala, and the prefrontal cortex, express high glucocorticoid receptors (GRs), these areas are the potential targets of stress hormones. Stress affects memory encoding, consolidation, and retrieval, which may depend on many factors such as the type, duration, the intensity of the stressor or the brain region. Here, this review mainly focused on the mechanisms involved in stress-induced memory impairment. Acute/chronic stress induces structural and functional changes in neurons and glial cells. Dendritic arborization, reduction of dendritic spine density, and alteration in glutamatergic-mediated synaptic transmission via N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are mechanisms that stress affect long-term memory formation. Exposure to acute or chronic stress could interplay with multiple neurotransmitter signaling, modulating the neuronal circuits involved in memory impairment or state-dependent learning. Stress hormones also modulate the expression of microRNAs in the specific brain regions responsible for stress-induced behaviors. Because of expressing GRs in astrocytes and microglial cells, stress could affect the morphology, structure, and functions of these glial cells in memory-related brain regions. Astrocytes play a crucial role in stress-induced aversive or fear memory formation. Over-activation of the microglial cells enhances the release of inflammatory cytokines, which results in neuronal injury. Stress has a prominent role in cognitive decline to induces memory problems, particularly in older adults. Due to the issue’s importance, here the provided overview attempted to address the question of how stress alters neuronal epigenetic regulators, synaptic transmissions, and glial activity in the brain.
Exposure to stressful conditions plays a critical role in brain processes, including neural plasticity, synaptic transmission, and cognitive functions. Since memory-related brain regions, the hippocampus (Hip), the amygdala, and the prefrontal cortex, express high glucocorticoid receptors (GRs), these areas are the potential targets of stress hormones. Stress affects memory encoding, consolidation, and retrieval, which may depend on many factors such as the type, duration, the intensity of the stressor or the brain region. Here, this review mainly focused on the mechanisms involved in stress-induced memory impairment. Acute/chronic stress induces structural and functional changes in neurons and glial cells. Dendritic arborization, reduction of dendritic spine density, and alteration in glutamatergic-mediated synaptic transmission via N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are mechanisms that stress affect long-term memory formation. Exposure to acute or chronic stress could interplay with multiple neurotransmitter signaling, modulating the neuronal circuits involved in memory impairment or state-dependent learning. Stress hormones also modulate the expression of microRNAs in the specific brain regions responsible for stress-induced behaviors. Because of expressing GRs in astrocytes and microglial cells, stress could affect the morphology, structure, and functions of these glial cells in memory-related brain regions. Astrocytes play a crucial role in stress-induced aversive or fear memory formation. Over-activation of the microglial cells enhances the release of inflammatory cytokines, which results in neuronal injury. Stress has a prominent role in cognitive decline to induces memory problems, particularly in older adults. Due to the issue’s importance, here the provided overview attempted to address the question of how stress alters neuronal epigenetic regulators, synaptic transmissions, and glial activity in the brain.
DOI: https://doi.org/10.37349/en.2022.00008
This article belongs to the special issue Neuroinflammation in the Ageing and the Injured Brain
