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- Volume 21, Issue 9, 2022
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 21, Issue 9, 2022
Volume 21, Issue 9, 2022
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Potential Protective Effect of Dl-3-n-butylphthalide on Chronic Cerebral Ischemia Brain Injury
Authors: Fangfang Zhao and Yumin LuoChronic cerebral ischemia is one of the common ischemic cerebrovascular diseases. Chronic cerebral ischemia can lead to brain dysfunction, and its pathophysiological mechanism involves inflammation, blood-brain barrier destruction, oxidative stress, and other factors. As it is difficult to detect, it is easily overlooked, and it is often only observed following the onset of cognitive dysfunction. At present, there are only a few drugs for its treatment. Dl-3-n-butylphthalide (NBP), a compound extracted from celery seed, may play an important role in protecting against brain damage caused by chronic cerebral ischemia. Therefore, here, we have paid attention to the prevention and treatment of chronic cerebral ischemia with NBP.
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Non-hepatic Hyperammonemia: A Potential Therapeutic Target for Sepsis-associated Encephalopathy
Authors: Lina Zhao, Yun Li, Yunying Wang, Zengzheng Ge, Huadong Zhu, Xiuhua Zhou and Yi LiSepsis-Associated Encephalopathy (SAE) is a common complication in the acute phase of sepsis, and patients who develop SAE have a higher mortality rate, longer hospital stay, and worse quality of life than other sepsis patients. Although the incidence of SAE is as high as 70% in sepsis patients, no effective treatment is available for this condition. To develop an effective treatment for SAE, it is vital to explore its pathogenesis. It is known that hyperammonemia is a possible factor in the pathogenesis of hepatic encephalopathy as ammonia is a potent neurotoxin. Furthermore, our previous studies indicate that non-hepatic hyperammonemia seems to occur more often in sepsis patients; it was also found that >50% of sepsis patients with non-hepatic hyperammonemia exhibited encephalopathy and delirium. Substatistical analyses indicate that non-hepatic hyperammonemia is an independent risk factor for SAE. This study updates the definition, clinical manifestations, and diagnosis of SAE; it also investigates the possible treatment options available for non-hepatic hyperammonemia in patients with sepsis and the mechanisms by which non-hepatic hyperammonemia causes encephalopathy.
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Immunotherapeutics for AD: A Work in Progress
Authors: Anuja Sharma, Jaspreet S. Anand and Yatender KumarAlzheimer's Disease (AD), often called the 'Plague of the 21st Century,' is a progressive, irreversible neurodegenerative disorder that leads to the degeneration and death of neurons. Multiple factors, such as genetic defects, epigenetic regulations, environmental factors, or cerebrovascular damage, are a manifestation of the neurodegenerative process that begins to occur decades before the onset of disease. To date, no treatment or therapeutic strategy has proven to be potent in inhibiting its progress or reversing the effects of the disease. The ever-increasing numbers and lack of sufficient therapies that can control or reverse the effects of the disease have propelled research in the direction of devising efficient therapeutic strategies for AD. This review comprehensively discusses the active and passive immunotherapies against Amyloid-β and Tau protein, which remain the popular choice of targets for AD therapeutics. Some of the prospective immunotherapies against Aβ plaques have failed due to various reasons. Much of the research is focused on targeting Tau, specifically, targeting the mid-region of extracellular Tau due to their potential to prevent seeding and hence the spread of neurofibrillary tangles (NFTs). Thus, there is a need to thoroughly understand the disease onset mechanisms and discover effective therapeutic strategies.
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Role of Vitamins in Neurodegenerative Diseases: A Review
Authors: Ravi R. Kumar, Lovekesh Singh, Amandeep Thakur, Shamsher Singh and Bhupinder KumarBackground: Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aβ plaques), neurodegeneration, and excitotoxicity. Methods: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. Conclusion: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer’s disease, there is a lack of vitamin- B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson’s disease, vitamin- D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, vitamin-C and vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.
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An Overview of Acute Flaccid Myelitis
Authors: Aseem Setia, Jasween Bhatia and Sankha BhattacharyaAcute Flaccid Myelitis is defined by the presence of Acute Flaccid Paralysis (AFP) and a spinal cord lesion on magnetic resonance imaging that is primarily limited to the grey matter. AFM is a difficult situation to deal with when you have a neurologic illness. According to the Centers for Disease Control and Prevention (CDC), a large number of cases were discovered in the United States in 2014, with 90% of cases occurring in children. Although the exact cause of AFM is unknown, mounting evidence suggests a link between AFM and enterovirus D68 (EV-D68). In 2014, an outbreak of AFM was discovered in the United States. The condition was initially linked to polioviruses; however, it was later found that the viruses were caused by non-polioviruses Enteroviruses D-68 (EV-D68). The number of cases has increased since 2014, and the disease has been declared pandemic in the United States. The sudden onset of muscle weakness, usually in an arm or leg, as well as pain throughout the body, the change in patient's facial expression (facial weakness), and shortness of breath, ingesting, and speaking are all common symptoms in patients suffering from neurologic disease. This article includes graphic and histogram representations of reported AFM incidents and criteria for causality, epidemiology, various diagnostic approaches, signs and symptoms, and various investigational guidelines. It also includes key statements about recent clinical findings related to AFM disease.
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A Critical Analysis of Quercetin as the Attractive Target for the Treatment of Parkinson's Disease
Parkinson's Disease (PD) is a multifaceted disorder with various factors suggested to play a synergistic pathophysiological role, such as oxidative stress, autophagy, pro-inflammatory events, and neurotransmitter abnormalities. While it is crucial to discover new treatments in addition to preventing PD, recent studies have focused on determining whether nutraceuticals will exert neuroprotective actions and pharmacological functions in PD. Quercetin, a flavonol-type flavonoid, is found in many fruits and vegetables and is recognised as a complementary therapy for PD. The neuroprotective effect of quercetin is directly associated with its antioxidant activity, in addition to stimulating cellular defence against oxidative stress. Other related mechanisms are activating Sirtuins (SIRT1) and inducing autophagy, in addition to induction of Nrf2-ARE and Paraoxonase 2 (PON2). Quercetin, whose neuroprotective activity has been demonstrated in many studies, unfortunately, has a disadvantage because of its poor water solubility, chemical instability, and low oral bioavailability. It has been reported that the disadvantages of quercetin have been eliminated with nanocarriers loaded with quercetin. The role of nanotechnology and nanodelivery systems in reducing oxidative stress during PD provides an indisputable advantage. Accordingly, the present review aims to shed light on quercetin's beneficial effects and underlying mechanisms in neuroprotection. In addition, the contribution of nanodelivery systems to the neuroprotective effect of quercetin is also discussed.
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COVID-19, the Brain, and the Future: Is Infection by the Novel Coronavirus a Harbinger of Neurodegeneration?
Authors: Adejoke Onaolapo and Olakunle OnaolapoThe possible impact of viral infections on the development or pathogenesis of neurodegenerative disorders remains largely unknown. However, there have been reports associating the influenza virus pandemic and long-term infection with the Japanese encephalitis virus with the development of post-encephalitic Parkinsonism or von Economo’s encephalitis. In the last couple of years, there has been a worldwide pandemic caused by the novel coronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which causes a severe acute respiratory syndrome and is found to be associated with symptoms or complications of the central nervous system. Its possible involvement with the central nervous system is in line with emerging scientific evidence stating that the human respiratory coronaviruses can enter the brain, infect neural cells, persist in the brain, and cause activation of myelin-reactive T cells. Currently, there is a dearth of scientific information on the acute or possible long-term impact of infection with SARS-CoV-2 on the development of dementia and/or neurodegenerative diseases. This is related to the fact that the virus is ‘new,’ and its effects on humans are still being studied. This narrative review examines the extant literature for understanding the impact of coronavirus infections on the brain as there is a possibility that coronavirus disease 2019 (COVID-19) could increase the risk for the development of neurodegenerative diseases or hasten their progression.
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Evaluation of Associated Genes with Traumatic Pain: A Systematic Review
Authors: Hamid R. Rasouli, Samira Talebi and Fathollah AhmadpourObjectives: The knowledge about the molecular pathway of traumatic pain relief is less documented. This systematic review study aimed to identify the genes and molecular pathways associated with various traumatic pains. Methods: The online databases such as EMBASE, MEDLINE, PubMed, Cochrane Library, International Clinical Trials Registry Platform, Clinical Trials, Google Scholar, Wiley, ISI Web of Knowledge, and Scopus were searched. Two review authors searched and screened all records' titles and abstracts, and the third expert reviewer author resolved their disagreement. The study’s design, various trauma injuries, types of genes, and molecular pathways were recorded. The genes and molecular pathways data were obtained via GeneCards®: The Human Gene Database (https://www.genecards.org). Results: Studies on a variety of trauma injuries regarding nerve and Spinal Cord Injuries (SCIs) (12 records), Hypertrophic scar with Severe Pain (one record), severe post-traumatic musculoskeletal pain (MSP) (one record), and orthopedic trauma (one record) were included. The main molecular pathways such as the immune system, apoptosis, and death receptor signaling, T-cell antigen receptor (TCR) signaling pathway, oxidative stress, interleukin(s) mediated signaling pathway, biological oxidations, metabolic pathways (especially amino acid metabolism and amino group), focal adhesion, the proliferation of vascular, epithelial, and connective tissue cells, angiogenesis and neural development were identified. Conclusion: The immune system, apoptosis, and metabolic pathways are crucial for understanding the roles of genes in traumatic pain. It is recommended that these identified pathways and related genes be considered therapeutical targets for pain management in patients with trauma injuries. In addition, different forms of trauma injuries require different pathways and related genes to be considered.
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Eugenol Elicits Prolongevity by Increasing Resistance to Oxidative Stress in C. elegans
Authors: Nikhat Parween, Amber Jabeen and Birendra PrasadAims: To analyze the efficacy of eugenol on longevity by assessing its antioxidant effect using Caenorhabditis elegans as an animal model. Background: Eugenol is a major polyphenolic component of Ocimum sanctum (Tulsi) which attributes wide pharmacological activities and can serve as a biomarker. However, the possible effect of eugenol on longevity in Caenorhabditis elegans has not been reported. Objective: The objective of this investigation was to provide the first scientific based results about the effect of eugenol on longevity, slowing down of paralysis in Alzheimer’s model and the mechanism behind it in Caenorhabditis elegans animal model system. Methods: The phenolic components of methanolic extract of Ocimum sanctum were analyzed by RP-HPLC. Worms were exposed to different concentrations of extract and one of its components - eugenol. Lifespan, health span, survival in CL4176 Alzheimer’s model and molecular mechanism were analyzed. Results: Extract of Ocimum sanctum and eugenol increased lifespan and provided indemnity against pro-oxidants. It also significantly improved healthy ageing and slowed the progression of neurodegeneration in CL4176 Alzheimer’s model of the worm by increasing survival against prooxidants and slowing down the paralysis. Longevity effect was independent of the DAF-16 as observed by using DAF-16::GFP and daf-16 null mutant strains. These results implicate eugenol as a potent therapeutic compound that may curtail ageing and age related disorders like- Alzheimer’s disease. Conclusion: The present work demonstrated eugenol as a potential anti-ageing compound that may curtail ageing, improve heath span by enhancing resistance to oxidative stress and exerts its effect independent of DAF-16 pathway. So, it can be assumed that eugenol can be beneficial to humans as well, albeit further research is necessary before declaring it for human consumption.
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Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders
Background: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. Hypothesis/Objective: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as Free Oxygen Radicals Test (FORT) and Free Oxygen Radicals Defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.
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Berberine Ameliorates Cognitive Impairment by Regulating Microglial Polarization and Increasing Expression of Anti-inflammatory Factors following Permanent Bilateral Common Carotid Artery Occlusion in Rats
Authors: Yue Tian, Yangmin Zheng, Qi Wang, Feng Yan, Zhen Tao, Fangfang Zhao, Yuqing Wang, Yuyou Huang, Fengjuan Li, Yitong Du, Ningqun Wang and Yumin LuoBackground: Chronic cerebral hypoperfusion is associated with vascular cognitive impairment, and there are no specific therapeutic agents for use in clinical practice. Berberine has demonstrated good neuroprotective effects in models of acute cerebral ischemia; however, whether it can alleviate cognitive impairment caused by chronic cerebral hypoperfusion has rarely been investigated. Objective: The present study aimed to explore the mechanism by which berberine alleviates cognitive impairment resulting from chronic cerebral hypoperfusion. Methods: Forty-two male Sprague-Dawley rats were randomly divided into three groups: sham, model, and berberine. The models of chronic cerebral hypoperfusion were established via permanent bilateral common carotid artery occlusion (BCCAO). Cognitive function was evaluated using the Morris water maze, while neuronal damage and microglial activation and polarization were evaluated using western blotting and immunofluorescence, respectively. Enzyme-linked immunosorbent assays were used to detect the expression of anti-inflammatory factors including interleukin- 4 (IL-4) and interleukin-10 (IL-10). Results: Rats exhibited cognitive dysfunction after BCCAO, which was significantly attenuated following the berberine intervention. Levels of synaptophysin and NeuN were decreased in states of chronic cerebral hypoperfusion, during which microglial activation and a transition from the M2 to M1 phenotype were observed. Berberine treatment also significantly reversed these features. Moreover, levels of IL-4 and IL-10 expression increased significantly after berberine treatment. Conclusion: Berberine may mitigate vascular cognitive dysfunction by promoting neuronal plasticity, inhibiting microglial activation, promoting transformation from an M1 to an M2 phenotype, and increasing levels of IL-4 and IL-10 expression.
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Volumes & issues
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Volume 23 (2024)
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Volume 22 (2023)
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Volume 21 (2022)
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Volume 20 (2021)
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Volume 19 (2020)
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Volume 18 (2019)
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Volume 17 (2018)
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Volume 16 (2017)
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Volume 15 (2016)
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Volume 14 (2015)
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Volume 13 (2014)
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Volume 12 (2013)
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Volume 11 (2012)
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Volume 10 (2011)
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Volume 9 (2010)
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Volume 8 (2009)
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Volume 7 (2008)
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Volume 6 (2007)
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Volume 5 (2006)