Exploration of neuroprotective therapy最新文献

{"title":"Efficacy of memantine compared with sodium valproate as prophylactic treatment for migraine: a controlled randomized pilot study","authors":"Damaris Vazquez-Guevara, Alejandro Orozco-Narvaez, Héctor G. Hernández-Rodríguez, F. Rivas-Ruvalcaba, J. Shiguetomi-Medina, Ildefonso Rodríguez-Leyva","doi":"10.37349/ent.2023.00042","DOIUrl":"https://doi.org/10.37349/ent.2023.00042","url":null,"abstract":"Aim: To compare the efficacy of memantine with that of valproate as a prophylactic treatment for episodic migraine within three months. The efficacy, safety, and response rate were evaluated.\u0000Methods: Prospective, randomized, double-blind, controlled clinical trial randomized participants were divided into two groups. The memantine group received memantine 10 mg twice daily, and the valproate group received valproate 500 mg twice daily.\u0000Results: Thirty-three patients participated in the study; 27 completed the treatment protocol, 14 in the memantine group, and 13 in the valproate group. The mean number of migraine attacks per month in the memantine group was 5.31 [standard deviation (SD) ± 1.54] initially and 0.93 (SD ± 1.49) at the end of treatment, noting a decrease of 4.21 (SD ± 1.76; P < 0.001). In the valproate group, the mean number of migraine attacks per month was 5.35 (SD ± 1.11) initially and 0.77 (SD ± 1.16) at the end of treatment, with a difference of 4.5 (SD ± 1.39; P < 0.001). All 27 patients had excellent response rates. Adverse effects were infrequent and mild in severity.\u0000Conclusions: A clinical trial compared the efficacy of memantine with that of valproate (first-line drug) as a prophylactic treatment. A significant reduction in attacks was noted in both drugs. Memantine could be a new preventive treatment option for migraine.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42496022","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}

{"title":"Innate and adaptive glial cell responses in Alzheimer’s disease","authors":"Ankita Singh, T. Singh","doi":"10.37349/ent.2023.00039","DOIUrl":"https://doi.org/10.37349/ent.2023.00039","url":null,"abstract":"Alzheimer’s disease (AD), which affects around twenty-seven million people globally, is an aging-related neurodegenerative condition characterized by the extracellular deposition of misfolded amyloid-β (Aβ) peptides and the intracellular production of neurofibrillary tangles (NFTs) AD results from the death of certain groups of neurons in the brain while appearing to have no impact on neighboring neurons. It is progressive and incurable. Therefore, the pathophysiology of afflicted populations and the development of intervention measures to stop neuronal cell death have been the main areas of attention for delineating therapeutic options. Proinflammatory cytokines are responsible for the stimulation of inflammatory responses and are mostly generated by activated macrophages in the brain. This review discusses how glial cells and innate and adaptive immune responses have a critical role in AD. It also provides information about microglial activation through the cluster of differentiation 40 (CD40) ligation and CD40L. CD40L ligation of microglial CD40 results in a large increase in tumor necrosis factor-α (TNF-α) production. Cultured cortical neuronal injury is caused when microglia are activated by CD40 ligation in the presence of interferon-γ (IFN-γ). This injury is significantly reduced by blocking the CD40 pathway or neutralising TNF-α. The management of AD would require integrating all available information about the innate and adaptive immune response affecting AD-related neuronal death.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44558565","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}

{"title":"The role of microbiota-gut-brain axis in neurodegenerative diseases: biochemical and therapeutic aspects","authors":"Januário T. Ernesto, Caio M. Damásio, V. S. Gontijo, J. Gasparotto, C. Viegas Jr.","doi":"10.37349/ent.2023.00038","DOIUrl":"https://doi.org/10.37349/ent.2023.00038","url":null,"abstract":"The enteric nervous system (ENS) is considered by some authors as the second human brain, given its fundamental role in the regulation process of the central nervous system (CNS). Recent data from scientific literature have shown the existence of close bidirectional communication between the gut microbiota and the CNS, influencing physiological and biochemical changes related to cognition, emotion, behavior, anxiety, depressive symptoms, and stress. Furthermore, the existence of mediators in the connection between intestinal microorganisms and the CNS is evident, which includes neural networks, signaling, immune, and endocrine responses. However, the mechanisms underlying the effects of gut microbiota on brain processes still need to be determined. Therefore, understanding the relationship between the gut and neurodegenerative diseases (NDs) is essential for developing effective prophylactic alternatives and disease-modifying drugs that can prevent or slow the progression of such diseases. Herein, this short review aimed to present the most recent data from the scientific literature associated with the physiological, biochemical, and cellular aspects involved in the interrelationship between the gut-brain axis and NDs, discussing the role of the intestinal microbiota, and its relationship with CNS disorders.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46655205","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}

{"title":"Neuroprotective agents in acute ischemic stroke","authors":"Grace YY Chia, S. Yeo, J. Ho, E. Jou, L. Yeo, B. Tan","doi":"10.37349/ent.2023.00037","DOIUrl":"https://doi.org/10.37349/ent.2023.00037","url":null,"abstract":"Acute ischemic stroke (AIS) is the leading cause of disability and one of the top causes of mortality worldwide. The current standard of care is reperfusion therapy including intravenous thrombolysis (IVT) and thrombectomy. However, these treatments have limitations as they have a limited therapeutic window. Hence, there is a vital need to develop neuroprotective agents to prevent brain injury, extend the reperfusion window, improve mortality, and reduce disability in AIS patients. Neuroprotective agents work by counteracting the detrimental biochemical and molecular events that result in irreversible ischemic damage. Numerous preclinical studies and clinical trials have been done on different agents. Thus far, all have been definitively unsuccessful in large trials. Currently, there are several challenges in translation from animal studies to human trials. It is important to understand the current evidence as well as past challenges in the development of neuroprotective strategies in AIS in order for a more strategic selection of agents to be studied, improve study designs and thus contribute to the development of effective neuroprotective agents. Newer agents have shown promise in neuroprotection, and human trials are ongoing. In this review, the mechanisms of action of different families of neuroprotective agents were discussed. The evidence for the efficacy of different drugs in each family of neuroprotective agents was also evaluated and the current research landscape in neuroprotection for AIS was summarized. The past challenges and limitations in clinical trials and proposed possible ways to address these issues were highlighted.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46708773","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}

{"title":"Can chronic therapeutic drug use by the elderly affect Alzheimer’s disease risk and rate of progression?","authors":"R. Franco, Joan Serrano-Marín","doi":"10.37349/ent.2023.00035","DOIUrl":"https://doi.org/10.37349/ent.2023.00035","url":null,"abstract":"There is no approved drug capable of halting the progression of the most prevalent neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD). Current therapeutic strategies focus mainly on the inhibition of the formation of protein aggregates and their deposition in the central nervous system. However, after almost a hundred years, proper management of the disease is still lacking. The fact of not finding effective management tools in the various clinical trials already carried out suggests that new hypotheses and strategies should be explored. Although vast resources have been allocated to the investigation of protein aggregates and the pathophysiology is now better understood, clues to the actual etiology are lacking. It is well known that brain homeostasis is of paramount importance for the survival of neurons. Drugs that target the periphery are often not subject to evaluation for their potential effect on the central nervous system. While acute treatments may be irrelevant, pills used for chronic conditions can be detrimental to neurons, especially in terms of progressive damage leading to a long-term decline in neuronal survival. Due to the lack of advances in the search for a curative treatment for neurodegenerative diseases, and the lack of new hypotheses about their etiology, a novel hypothesis is here proposed. It consists of assuming that the effects of the drugs most commonly used by the elderly, such as antihypertensive, hypoglycemic, and hypocholesterolemic, could have a negative impact on neuronal survival.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43389122","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}

{"title":"Pathophysiology of non-motor signs in Parkinson’s disease: some recent updating with brief presentation","authors":"K. Radad, R. Moldzio, C. Krewenka, B. Kranner, W. Rausch","doi":"10.37349/ent.2023.00036","DOIUrl":"https://doi.org/10.37349/ent.2023.00036","url":null,"abstract":"Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting 1% of the population above sixty years. It is caused by an interaction between genetic and environmental risk factors. Loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) is pathologically characterizing the disease and responsible for the cardinal motor symptoms, most notably, bradykinesia, rest tremors, rigidity, and loss of postural reflexes. Non-motor signs such as olfactory deficits, cognitive impairment, sleep behavior disorders, and gastrointestinal disturbances are reflecting disturbances in the non-dopaminergic system. They precede dopaminergic neuronal degenerations by 5–10 years and are considered the main contributors to patients’ disability, particularly after the successful implementation of levodopa (L-dopa) treatment of motor symptoms. The present general review aimed to briefly update non-motor signs and their underlying pathophysiology in PD.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47703629","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}

{"title":"Machine learning as a new tool in neurological disease prevention, diagnosis, and treatment","authors":"C. Volonté","doi":"10.37349/ent.2023.00034","DOIUrl":"https://doi.org/10.37349/ent.2023.00034","url":null,"abstract":"More than 600 different neurological diseases affect the human population. Some of these are genetic and can emerge even before birth, and some are caused by defects, infections, trauma, degeneration, inflammation, and cancer. However, they all share disabilities caused by damage to the nervous system. In the last decades, the burden of almost all neurological disorders has increased in terms of absolute incidence, prevalence, and mortality, largely due to the population’s growth and aging. This represents a dangerous trend and should become our priority for the future. But what new goals are we going to set and reach now, and how will we exploit thought-provoking technological skills for making these goals feasible? Machine learning can be at the root of the problem. Indeed, most recently, there has been a push towards medical data analysis by machine learning, and a great improvement in the training capabilities particularly of artificial deep neural networks (DNNs) inspired by the biological neural networks characterizing the human brain. This has generated competitive results for applications such as biomolecular target and protein structure prediction, structure-based rational drug design, and repurposing, all exerting a major impact on neuroscience and human well-being. By approaching early risks for diseases, non-invasive diagnosis, personalized treatment assessment, drug discovery, and automated science, the machine learning arena has thus the potential of becoming the new frontier for empowering neuroscience research and clinical practice in the years ahead.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47622095","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}

{"title":"Tension pneumocephalus as a complication of surgical evacuation of chronic subdural hematoma: case report and literature review.","authors":"Mohammed A Azab, Ahmed Hazem, Brandon Lucke-Wold","doi":"10.37349/ent.2023.00046","DOIUrl":"10.37349/ent.2023.00046","url":null,"abstract":"<p><p>The management of symptomatic chronic subdural hematoma (CSDH) is surgical evacuation and prognosis in most cases is good. Tension pneumocephalus is the presence of air under pressure in the intracranial cavity. A case of tension pneumocephalus developing as a complication of burr hole evacuation of CSDH is illustrated. In this case, tension pneumocephalus was managed by reopening the wound and saline irrigation with a subdural drain placement. Considering this case report and after a careful review of the literature, the physiopathology, diagnosis, and treatment of this complication are highlighted in the article.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":"3 4","pages":"177-185"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171638","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}

{"title":"Neuroprotective astroglial response to neural damage and its relevance to affective disorders.","authors":"José Javier Miguel-Hidalgo","doi":"10.37349/ent.2023.00054","DOIUrl":"10.37349/ent.2023.00054","url":null,"abstract":"<p><p>Astrocytes not only support neuronal function with essential roles in synaptic neurotransmission, action potential propagation, metabolic support, or neuroplastic and developmental adaptations. They also respond to damage or dysfunction in surrounding neurons and oligodendrocytes by releasing neurotrophic factors and other molecules that increase the survival of the supported cells or contribute to mechanisms of structural and molecular restoration. The neuroprotective responsiveness of astrocytes is based on their ability to sense signals of degeneration, metabolic jeopardy and structural damage, and on their aptitude to locally deliver specific molecules to remedy threats to the molecular and structural features of their cellular partners. To the extent that neuronal and other glial cell disturbances are known to occur in affective disorders, astrocyte responsiveness to those disturbances may help to better understand the roles astrocytes play in affective disorders. The astrocytic sensing apparatus supporting those responses involves receptors for neurotransmitters, purines, cell adhesion molecules and growth factors. Astrocytes also share with the immune system the capacity of responding to cytokines released upon neuronal damage. In addition, in responses to specific signals astrocytes release unique factors such as clusterin or humanin that have been shown to exert potent neuroprotective effects. Astrocytes integrate the signals above to further deliver structural lipids, removing toxic metabolites, stabilizing the osmotic environment, normalizing neurotransmitters, providing anti-oxidant protection, facilitating synaptogenesis and acting as barriers to contain varied deleterious signals, some of which have been described in brain regions relevant to affective disorders and related animal models. Since various of the injurious signals that activate astrocytes have been implicated in different aspects of the etiopathology of affective disorders, particularly in relation to the diagnosis of depression, potentiating the corresponding astrocyte neuroprotective responses may provide additional opportunities to improve or complement available pharmacological and behavioral therapies for affective disorders.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":"3 5","pages":"328-345"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rehabilitation for non-motor symptoms for patients with Parkinson's disease from an α-synuclein perspective: a narrative review.","authors":"Zhaoyang Liu,&nbsp;Jessica Lemus,&nbsp;Irina V Smirnova,&nbsp;Wen Liu","doi":"10.37349/ent.2023.00049","DOIUrl":"10.37349/ent.2023.00049","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative disorder affecting aged population around the world. PD is characterized by neuronal Lewy bodies present in the substantia nigra of the midbrain and the loss of dopaminergic neurons with various motor and non-motor symptoms associated with the disease. The protein α-synuclein has been extensively studied for its contribution to PD pathology, as α-synuclein aggregates form the major component of Lewy bodies, a hallmark of PD. In this narrative review, the authors first focus on a brief explanation of α-synuclein aggregation and circumstances under which aggregation can occur, then present a hypothesis for PD pathogenesis in the peripheral nervous system (PNS) and how PD can spread to the central nervous system from the PNS via the transport of α-synuclein aggregates. This article presents arguments both for and against this hypothesis. It also presents various non-pharmacological rehabilitation approaches and management techniques for both motor and non-motor symptoms of PD and the related pathology. This review seeks to examine a possible hypothesis of PD pathogenesis and points to a new research direction focus on rehabilitation therapy for patients with PD. As various non-motor symptoms of PD appear to occur earlier than motor symptoms, more focus on the treatment of non-motor symptoms as well as a better understanding of the biochemical mechanisms behind those non-motor symptoms may lead to better long-term outcomes for patients with PD.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":"235-257"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42393971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}