Exploration of neuroprotective therapy最新文献

{"title":"Combined effects of dry needling and exercises therapy on muscle spasticity and motor function in chronic stroke: a pretest-posttest pilot study","authors":"Seyedeh Saeideh Babazadeh-Zavieh, N. N. Ansari, N. Ghotbi, S. Naghdi, Seyed Mohammad Jafar Haeri, M. Khanmohammadi, K. Mansouri","doi":"10.37349/ent.2022.00021","DOIUrl":"https://doi.org/10.37349/ent.2022.00021","url":null,"abstract":"Aim: Spasticity is one of the most common symptoms in post-stroke patients. Dry needling (DN) is a relatively new method for the management of muscle spasticity. A multimodal treatment may be more effective in spasticity management. The purpose of this study was to explore the short-term combined effects of DN and exercise therapy on wrist flexor spasticity, motor function, and motor neuron excitability in patients with chronic stroke. Methods: Ten patients with stroke and a mean age of 52 ± 4.9 years participated in this pretest-posttest pilot study. Patients received four sessions of DN and exercise therapy. Affected flexor carpi radialis and flexor carpi ulnaris muscles were needled each for 1 min. Patients underwent exercise therapy for about 30 min, once a week after DN. The outcome measures were the Modified Modified Ashworth Scale (MMAS), the maximal amplitude of H wave/maximal amplitude of M wave ratio (Hmax/Mmax Ratio), H-reflex latency, wrist extension active and passive range of motion (ROM), Action Research Arm Test (ARAT), and Fugl-Meyer Assessment (FMA). Assessments were performed at baseline, after four sessions of treatment, and three weeks after treatment. Results: After treatment, significant improvements in MMAS, wrist passive ROM, ARAT, and FMA were obtained (P ≤ 0.05). Conclusions: DN combined with exercise therapy improved muscle spasticity and motor function in patients with chronic stroke. Further investigations with a randomized controlled trial design with a comparator group of DN only are warranted (https://www.irct.ir/; IRCT ID: IRCT20180611040061N1).","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42076424","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 meditation-based approaches improve the cleansing power of the glymphatic system?","authors":"P. Wostyn, Piet Goddaer","doi":"10.37349/ent.2022.00022","DOIUrl":"https://doi.org/10.37349/ent.2022.00022","url":null,"abstract":"The glymphatic system, first described in 2012, is a brain-wide perivascular network that plays an important role in promoting interstitial metabolic waste removal from the brain. Glymphatic pathway function has been reported to be dramatically diminished in the aging brain. Furthermore, glymphatic system dysfunction has been linked to a spectrum of neurodegenerative diseases including Alzheimer’s disease (AD). This waste clearance pathway of the brain is most active during sleep and is largely disengaged during wakefulness. While norepinephrine (NE) is responsible for suppressing the glymphatic function, electroencephalographic slow-wave (delta) activity has a facilitating effect. An intriguing question is whether these regulators of glymphatic activity can be modulated by meditation-based approaches and whether such approaches have the ability to increase glymphatic function in the awake brain. The present article hypothesizes that meditation-based approaches, such as immersive sound meditation, may have the potential to enhance glymphatic pathway transport and solute clearance by reducing NE and increasing slow-wave activity. If confirmed, meditation could be an attractive approach to promoting healthy brain aging and to preventing neurodegenerative conditions like AD.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48610238","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":"Gut microbiota could modulate the effects of neuro-immune responses and memory traces via the gut-brain-immune axis in schizophrenia","authors":"Haruka Sawamura, Kurumi Taniguchi, Yuka Ikeda, Ai Tsuji, Y. Kitagishi, S. Matsuda","doi":"10.37349/ent.2022.00019","DOIUrl":"https://doi.org/10.37349/ent.2022.00019","url":null,"abstract":"Altered immunity may have destructive consequences for the integrated central nervous system. This immune response often affects progressive neurodegenerative diseases such as Parkinson’s disease and/or psychiatric disorders such as schizophrenia. In particular, schizophrenia pathogenesis may be mediated by multiple neuro-immune interaction pathways. Gut microbiota might affect the brain and/or immune function. Significant machineries of immunity are commonly affected by the commensal gut microbiota. Therefore, schizophrenia may be connected with the gut-immune system. In addition, the brain and immune systems cooperate on multiple levels. The brain could save several pieces of information about specific inflammation in a body. This immunological memory named “engrams”, also called memory traces, could restore the initial disease state, which may help to explain key features of schizophrenia. Based on this concept, therapeutic strategies for schizophrenia could be the modification of the gut microbiota. Probiotics and/or fecal microbiota transplantation are now emerging as the most promising treatments for the modification. More consideration of the roles of gut microbiota will conduct the further development of immune-based therapeutics for the prevention and/or treatments of psychiatric disorders.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47113938","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":"Various facets of excitotoxicity","authors":"T. Glaser, J. B. Silva, Guilherme Juvenal, Pedro Negrão Maiolini, Natalia Turrini, L. Petiz, L. B. Marques, D. Ribeiro, Qing Ye, Yong Tang, H. Ulrich","doi":"10.37349/ent.2022.00017","DOIUrl":"https://doi.org/10.37349/ent.2022.00017","url":null,"abstract":"Aim:\u0000\u0000Excitotoxicity results from unusually increased activation of excitatory amino acid receptors leading to neuronal death. Since glutamate is the main excitatory neurotransmitter in the central nervous system, it is also the most common excitotoxicity trigger. This uncontrolled neuronal response participates in various neurodegenerative diseases, such as ischemia, hypoglycemia, Huntington’s, Parkinson’s and Alzheimer’s disease. Thus, the investigation in the field expanded a lot in the past decade, leading to in vitro modelling adaptations. However, much performed work on glutamate-induced excitotoxicity is methodologically inconsistent in the literature. The field lacks reproducibility, which is one of the main fundaments of empirical science. In this regard, the literature was summarized and the main methodological features were critically evaluated, aiming to guide the researchers that are starting in the field.\u0000Methods:\u0000\u0000Published data since 1985 from PUBMED were collected and analyzed to observe which in vitro experimental conditions of excitotoxicity were reproducible. The suggested methods were based on the characteristics of excitotoxicity, such as abnormal intracellular calcium mediated signaling, mitochondria impairment, reactive oxygen species accumulation and cell death. Various conditions and comparative controls were used to design the standard investigation of excitotoxicity, such as culture medium content (presence of glutamate and aspartate), time interval of induction and the concentration of the inductor, based on the most reproducible published ones.\u0000Results:\u0000\u0000Our results and critical analysis point to some experimental conditions to consider, such as primary cultured neurons are more sensitive to glutamate and the response obtained is more robust than in other models; excitotoxicity mediated effects are better observed one hour following the stimulus; the culture medium should contain low levels of glutamate or aspartate or glycine. Online available phosphoproteomic data on excitotoxicity using the primary cortical neurons in vitro model supported the same conditions proposed by us.\u0000Conclusions:\u0000\u0000This manuscript will facilitate the design of any research for excitotoxic or neuroprotective compounds in physiological and pathophysiological conditions by standardizing and improving experimental conditions.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43569381","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":"Dry needling in stroke","authors":"N. Surya, G. Ramamurthy","doi":"10.37349/ent.2022.00016","DOIUrl":"https://doi.org/10.37349/ent.2022.00016","url":null,"abstract":"Stroke causes acute neurological deficit which is an important cause of morbidity and mortality. Neurorehabilitation is an important dimension in the management of post-stroke deficits. Spasticity, pain, and neurological deficits are contributors to post-stroke disability. Dry needling (DN) is a technique commonly used in the management of myofascial pain. Recent evidence suggests its efficacy in the management of post-stroke disability. The descriptive review on the use of DN summarises the evidence for the management of post-stroke patients such as spasticity, balance, pain, functional outcome, tremor, and ultrasonographic evidence. The filiform needle is inserted into the target muscle until a local twitch response is obtained. The effects of DN are produced by the local stretch of the spastic muscle and afferent modulation of the reflex arc that decreases the excitability of the alpha motor neuron. The DN reduces muscle spasticity in post-stroke patients. The improved spasticity is translated to better functional outcomes and balance. The procedure is also shown to reduce pain including post-stroke shoulder pain. It is also shown to improve tremors in post-stroke patients. Ultrasonographic evidence of the beneficial effects of DN shows improved measures in the pennate angle and mean muscle thickness. Concurrent use of DN and electrical stimulation improve spasticity, the effect which may be seen for longer periods. DN is emerging as a useful and cost-effective technique in the management of post-stroke patients. The evidence for the use of DN in the management of post-stroke spasticity is high. However, more research is required to assess its efficacy in functional outcomes and other aspects of the stroke.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45767987","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":"Balancing cholesterol in the brain: from synthesis to disposal","authors":"Lydia Qian, Amanda B. Chai, I. Gelissen, Andrew J. Brown","doi":"10.37349/ent.2022.00015","DOIUrl":"https://doi.org/10.37349/ent.2022.00015","url":null,"abstract":"The cholesterol is a vital component of cell membranes and myelin sheaths, and a precursor for essential molecules such as steroid hormones. In humans, cholesterol is partially obtained through the diet, while the majority is synthesized in the body, primarily in the liver. However, the limited exchange between the central nervous system and peripheral circulation, due to the presence of the blood-brain barrier, necessitates cholesterol in the brain to be exclusively acquired from local de novo synthesis. This cholesterol is reutilized efficiently, rendering a much slower overall turnover of the compound in the brain as compared with the periphery. Furthermore, brain cholesterol is regulated independently from peripheral cholesterol. Numerous enzymes, proteins, and other factors are involved in cholesterol synthesis and metabolism in the brain. Understanding the unique mechanisms and pathways involved in the maintenance of cholesterol homeostasis in the brain is critical, considering perturbations to these processes are implicated in numerous neurodegenerative diseases. This review focuses on the developing understanding of cholesterol metabolism in the brain, discussing the sites and processes involved in its synthesis and regulation, as well as the mechanisms involved in its distribution throughout, and elimination from, the brain.","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41790169","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 glymphatic system and subarachnoid hemorrhage: disruption and recovery.","authors":"Stephan Quintin, Arnav Barpujari, Yusuf Mehkri, Jairo Hernandez, Brandon Lucke-Wold","doi":"10.37349/ent.2022.00023","DOIUrl":"10.37349/ent.2022.00023","url":null,"abstract":"<p><p>The glymphatic system, or glial-lymphatic system, is a waste clearance system composed of perivascular channels formed by astrocytes that mediate the clearance of proteins and metabolites from the brain. These channels facilitate the movement of cerebrospinal fluid throughout brain parenchyma and are critical for homeostasis. Disruption of the glymphatic system leads to an accumulation of these waste products as well as increased interstitial fluid in the brain. These phenomena are also seen during and after subarachnoid hemorrhages (SAH), contributing to the brain damage seen after rupture of a major blood vessel. Herein this review provides an overview of the glymphatic system, its disruption during SAH, and its function in recovery following SAH. The review also outlines drugs which target the glymphatic system and may have therapeutic applications following SAH.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":"2 3","pages":"118-130"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40402014","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":"Subarachnoid hemorrhage: management considerations for COVID-19.","authors":"Eric J Panther, Brandon Lucke-Wold","doi":"10.37349/ent.2022.00018","DOIUrl":"10.37349/ent.2022.00018","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) has deleterious outcomes for patients, and during the hospital stay, patients are susceptible to vasospasm and delayed cerebral ischemia. Coronavirus disease 2019 (COVID-19) has been shown to worsen hypertension through angiotensin-converting enzyme 2 (ACE2) activity, therefore, predisposing to aneurysm rupture. The classic renin-angiotensin pathway activation also predisposes to vasospasm and subsequent delayed cerebral ischemia. Matrix metalloproteinase 9 upregulation can lead to an inflammatory surge, which worsens outcomes for patients. SAH patients with COVID-19 are more susceptible to ventilator-associated pneumonia, reversible cerebral vasoconstriction syndrome, and respiratory distress. Emerging treatments are warranted to target key components of the anti-inflammatory cascade. The aim of this review is to explore how the COVID-19 virus and the intensive care unit (ICU) treatment of severe COVID can contribute to SAH.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":"2 1","pages":"65-73"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43704543","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":"Targeting cytochrome P450 46A1 and brain cholesterol 24-hydroxylation to treat neurodegenerative diseases.","authors":"Irina A Pikuleva","doi":"10.37349/ent.2021.00013","DOIUrl":"https://doi.org/10.37349/ent.2021.00013","url":null,"abstract":"<p><p>The brain cholesterol content is determined by the balance between the pathways of <i>in situ</i> biosynthesis and cholesterol elimination <i>via</i> 24-hydroxylation catalyzed by CYP46A1 (cytochrome P450 46A1). Both pathways are tightly coupled and determine the rate of brain cholesterol turnover. Evidence is accumulating that modulation of CYP46A1 activity by gene therapy or pharmacologic means could be beneficial in case neurodegenerative and other brain diseases and affect brain processes other than cholesterol biosynthesis and elimination. This minireview summarizes these other processes, most common of which include abnormal protein accumulation, memory and cognition, motor behavior, gene transcription, protein phosphorylation as well as autophagy and lysosomal processing. The unifying mechanisms, by which these processes could be affected by CYP46A targeting are also discussed.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":"159-172"},"PeriodicalIF":0.0,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835717/pdf/nihms-1765082.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39916414","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":"Blocking cholesterol storage to treat Alzheimer's disease.","authors":"Ta Yuan Chang, Catherine C Y Chang, Taylor C Harned, Adrianna L De La Torre, Junghoon Lee, Thao N Huynh, James G Gow","doi":"10.37349/ent.2021.00014","DOIUrl":"10.37349/ent.2021.00014","url":null,"abstract":"<p><p>Cholesterol serves as an essential lipid molecule in various membrane organelles of mammalian cells. The metabolites of cholesterol also play important functions. Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), also named as sterol <i>O</i>-acyltransferase 1, is a membrane-bound enzyme residing at the endoplasmic reticulum (ER). It converts cholesterol to cholesteryl esters (CEs) for storage, and is expressed in all cells. CEs cannot partition in membranes; they can only coalesce as cytosolic lipid droplets. Excess CEs are found in the vulnerable region of the brains of patients with late-onset Alzheimer's disease (AD), and in cell and mouse models for AD. Reducing CE contents by genetic inactivation of <i>ACAT1</i>, or by pharmacological inhibition of ACAT is shown to reduce amyloidopathy and other hallmarks for AD. To account for the various beneficial actions of the ACAT1 blockade (A1B), a working hypothesis is proposed here: the increase in CE contents observed in the AD brain is caused by damages of cholesterol-rich lipid rafts that are known to occur in neurons affected by AD. These damages cause cholesterol to release from lipid rafts and move to the ER where it will be converted to CEs by ACAT1. In addition, the increase in CE contents may also be caused by overloading with cholesterol-rich substances, or through activation of <i>ACAT1</i> gene expression by various proinflammatory agents. Both scenarios may occur in microglia of the chronically inflamed brain. A1B ameliorates AD by diverting the cholesterol pool destined for CE biosynthesis such that it can be utilized more efficiently to repair membrane damage in various organelles, and to exert regulatory actions more effectively to defend against AD. To test the validity of the A1B hypothesis in cell culture and <i>in vivo</i>, the current status of various anti-ACAT1 agents that could be further developed is briefly discussed.</p>","PeriodicalId":73000,"journal":{"name":"Exploration of neuroprotective therapy","volume":" ","pages":"173-184"},"PeriodicalIF":0.0,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39645522","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}