Utku Aykan, Muhammed Cihan Güvel, Gokcen Paykal, Canan Uluoglu
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.
{"title":"Neuropharmacologic modulation of the melatonergic system","authors":"Utku Aykan, Muhammed Cihan Güvel, Gokcen Paykal, Canan Uluoglu","doi":"10.37349/en.2023.00029","DOIUrl":"https://doi.org/10.37349/en.2023.00029","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138946032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oğuzhan Birdal, E. Calik, Ümit Arslan, Y. Koza, Uğur Kaya, A. Çolak, M. Hakan Taş
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.
目的：缺血性脑卒中的主要危险因素之一是颈动脉明显狭窄，颅外重度颈动脉狭窄占缺血性脑卒中的20%。在颈动脉支架植入术（CAS）问世之前，颈动脉狭窄唯一有效、可靠的治疗方法是颈动脉内膜剥脱术（CEA）。本研究比较了CAS和CEA对颈动脉明显狭窄患者的治疗效果：2018年至2022年间，对该院接受颈动脉血运重建术的所有患者的住院病历进行回顾性分析。根据颈动脉血运重建是实施CEA还是CAS，将患者分为两组。为了减少偏差，对两组患者的基线临床特征进行了倾向评分匹配。为了比较30天、1年和长期结果，对短暂性脑缺血发作（TIA）、心肌梗死、中风、全因死亡率和复合终点进行了分析：PSM后，CEA组和CAS组各76名患者进行了比较。平均年龄为 69.80 岁 ± 11.35 岁，121 人（80%）为男性。患者的平均随访时间为（33 个月± 6 个月）。CAS组围手术期的TIA发生率[9 (12%) vs. 4 (5%)；P < 0.05]、TIA发生率和1年后的综合终点[分别为11 (15%) vs. 2 (3%)；P < 0.05和27 (36%) vs. 16 (21%)；P < 0.05]明显高于CEA组。结论：结论：在对严重颈动脉狭窄病例的检查中，CEA组和CAS组在1个月、1年结果（TIA和综合终点除外）和长期结果方面没有明显差异。颅外颈动脉狭窄也可以通过 CAS 得到安全有效的治疗。
{"title":"Carotid endarterectomy compared with carotid artery stenting for extracranial carotid artery stenosis: a retrospective single-centre study","authors":"Oğuzhan Birdal, E. Calik, Ümit Arslan, Y. Koza, Uğur Kaya, A. Çolak, M. Hakan Taş","doi":"10.37349/en.2023.00027","DOIUrl":"https://doi.org/10.37349/en.2023.00027","url":null,"abstract":"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.\u0000Methods: 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.\u0000Results: 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.\u0000Conclusions: 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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"16 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138972516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Stigma and psychosocial problems in patients with epilepsy","authors":"Kubra Yeni","doi":"10.37349/en.2023.00026","DOIUrl":"https://doi.org/10.37349/en.2023.00026","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"54 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138597664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature","authors":"H. Goischke","doi":"10.37349/en.2023.00020","DOIUrl":"https://doi.org/10.37349/en.2023.00020","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84876641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Modify gut microbiome in autism: a promising strategy?","authors":"J. Demarquoy, Haifa Othman, Caroline Demarquoy","doi":"10.37349/en.2023.00018","DOIUrl":"https://doi.org/10.37349/en.2023.00018","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88802329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Soliman, Khaled Mowafy, Mostafa Abd Elgwad, Rosan Soliman, R. Soliman
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.
{"title":"Covered stent graft for treatment of carotid artery stenosis with post-stenotic aneurysm","authors":"M. Soliman, Khaled Mowafy, Mostafa Abd Elgwad, Rosan Soliman, R. Soliman","doi":"10.37349/en.2023.00019","DOIUrl":"https://doi.org/10.37349/en.2023.00019","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84271709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Circadian regulation of the immune-hematopoietic system","authors":"G. Maestroni","doi":"10.37349/en.2023.00017","DOIUrl":"https://doi.org/10.37349/en.2023.00017","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86607953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michelli Ramires Teixeira, A.L. Alievi, Vitor Rodrigues da Costa, João Rafael Dias Pinto, R. P. Araldi
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.
{"title":"Therapeutic potential of extracellular vesicles in Parkinson’s disease","authors":"Michelli Ramires Teixeira, A.L. Alievi, Vitor Rodrigues da Costa, João Rafael Dias Pinto, R. P. Araldi","doi":"10.37349/en.2023.00016","DOIUrl":"https://doi.org/10.37349/en.2023.00016","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88407314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Mesenchymal stem cell stroke therapy: current limitations in its clinical translation","authors":"Ylenia Pastorello, M. Slevin","doi":"10.37349/en.2023.00015","DOIUrl":"https://doi.org/10.37349/en.2023.00015","url":null,"abstract":"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.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86101043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuroinflammation plays a key role in the pathogenesis of post-cardiac arrest (CA) brain injury. Innate immune cells sense a variety of danger signals through pattern-recognition receptors and evoke rapidly after ischemic challenge, triggering inflammatory responses and amplifying brain damage. A programmed cell death (PCD) pathway is activated after ischemic and/or inflammatory stimuli, leading to the elimination of the damaged cells. However, PCD also regulates inflammatory responses flexibly. The present review aimed to summarize the mechanisms of inflammatory responses, including the biology of immune cells, the innate immune recognition that initiates the inflammation, and the immunomodulatory effects of PCD following CA. Promising therapeutic approaches of targeting inflammatory responses to alleviate brain injury and improve neurological outcomes after CA are also reviewed.
{"title":"Inflammatory responses involved in post-cardiac arrest brain injury: mechanisms, regulation, and therapeutic potential","authors":"Yuzhen Zhang, Zhentong Li, Kunxue Zhang, Yuan Chang, Jiancong Chen, Murad Al-Nusaif, Suyue Pan, Kaibin Huang","doi":"10.37349/en.2023.00014","DOIUrl":"https://doi.org/10.37349/en.2023.00014","url":null,"abstract":"Neuroinflammation plays a key role in the pathogenesis of post-cardiac arrest (CA) brain injury. Innate immune cells sense a variety of danger signals through pattern-recognition receptors and evoke rapidly after ischemic challenge, triggering inflammatory responses and amplifying brain damage. A programmed cell death (PCD) pathway is activated after ischemic and/or inflammatory stimuli, leading to the elimination of the damaged cells. However, PCD also regulates inflammatory responses flexibly. The present review aimed to summarize the mechanisms of inflammatory responses, including the biology of immune cells, the innate immune recognition that initiates the inflammation, and the immunomodulatory effects of PCD following CA. Promising therapeutic approaches of targeting inflammatory responses to alleviate brain injury and improve neurological outcomes after CA are also reviewed.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78512737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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