Neuroprotection最新文献

{"title":"Rapid eye movement sleep deprivation induced gene regulation for modulation of noradrenaline level in brain regions of rats: Implications with chronic sleep-loss associated pathophysiological conditions.","authors":"Rachna Mehta, Raghavendra Murali, Birendra Nath Mallick","doi":"10.1002/nep3.70018","DOIUrl":"10.1002/nep3.70018","url":null,"abstract":"<p><strong>Background: </strong>Rapid eye movement sleep (REMS) loss affects almost all physiological processes, while it itself is affected in disorders. REMS maintains optimum level of noradrenaline (NA) in a healthy individual, while increased NA during disturbed REMS is associated with diseases. The synthesis, release, and degradation of neurotransmitter are modulated by biomolecules, which are genetically encoded. The aim of this study is to understand the transcriptional and translational changes of those biomolecules in locus coeruleus (LC) and pedunculo-pontine tegmentum (PPT) in association with REMS and its loss, which is expected to help us explain associated acute and chronic pathophysiological changes.</p><p><strong>Methods: </strong>In this study, male inbred Wistar rats were deprived of REMS for 96 h using classical flowerpot method; free-moving-, large platform- and recovery-control sets were also conducted (<i>n</i> = 5 per group). Brain areas related to REMS regulation, namely the LC and PPT, as well as an area unrelated to REMS regulation, namely the hippocampus, were dissected out for evaluation. Animals were grouped based on similar traits (age, weight, etc.) and then randomly by random table assigned within those matched sets. Dopamine β-hydroxylase (DBH), tyrosine hydroxylase (TH), and monoamine oxidase-A (MAO-A) protein, their gene expressions and associated histone modifications were evaluated using western blot analysis, quantitative polymerase chain reaction (qPCR) and chromatin immunoprecipitation (ChIP) assays, respectively. One-way analysis of variance (ANOVA) followed by Holm Sidak multiple comparison test was applied to evaluate the significance level between the experimental and control groups using GraphPad Prism (version 9.0.0; GraphPad Software, San Diego, California, USA, www.graphpad.com) and Sigma Stat Statistical Software (version 12; Jandel Scientific Software, CA, USA).</p><p><strong>Results: </strong>Upon rapid eye movement sleep deprivation (REMSD), although TH and DBH protein expressions altered significantly in all the brain areas, the latter was highest in LC (F<sub>(5,30)</sub> = 11.320, <i>p</i> < 0.001); MAO-A decreased in LC (F<sub>(5,30)</sub> = 9.286, <i>p</i> < 0.001). In LC, <i>DBH</i> (F<sub>(8,44)</sub> = 7.138, <i>p</i> < 0.001) and <i>TH</i> (F<sub>(8,44)</sub> = 5.813, <i>p</i> < 0.001) gene expressions and histone H3 at lysine 14 (H3K14)-acetylation of <i>TH</i> (F<sub>(11,59)</sub> = 25.290, <i>p</i> < 0.001) and <i>DBH</i> (F<sub>(11,59)</sub> = 11.610, <i>p</i> < 0.001) increased, while lysine K9 in histone H3 (H3K9)-dimethylation tended to decrease, whereas opposite modifications were seen in <i>MAO-A</i> gene expression (F<sub>(11,59)</sub> = 16.970, <i>p</i> < 0.001). The altered gene- and protein-expressions returned or tended to return to normal levels after recovery, as in post-REMSD prazosin treated rat brains.</p><p><strong>Conclusion: </strong>The differential expressions of","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 4","pages":"370-385"},"PeriodicalIF":4.1,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890264","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":"Exploiting glial cell functions for neurodegeneration therapy.","authors":"Tobiloba S Olajide","doi":"10.1002/nep3.70020","DOIUrl":"10.1002/nep3.70020","url":null,"abstract":"<p><p>Glial cells, alongside neurons, are the major cells of the central nervous system. More than just supporting neurons, glial cells are vital in central nervous system homeostasis and actively shape neurodegenerative disease mechanisms. They exhibit dual roles in promoting neuroprotection through glutamate clearance, mitochondrial transfer, extracellular vesicle signaling, and remyelination, yet also contributing to excitotoxicity, neuroinflammation, and myelin loss. Recent studies emphasize their therapeutic potential, such as enhancing excitatory amino acid transporters, engineering extracellular vesicles, and boosting oligodendrocyte precursor cell function in combating neurodegeneration. This mini review comments on previous articles published in <i>Neuroprotection</i> alongside others, and discusses how enhancing glial protective roles may serve as novel neuroprotective interventions.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 4","pages":"353-357"},"PeriodicalIF":4.1,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890229","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":"Better understanding complex pathomechanisms in central nervous system disorders as a prerequisite for improved diagnostic and therapeutic approaches.","authors":"Piotr Walczak, Shen Li, Xunming Ji, Johannes Boltze","doi":"10.1002/nep3.70017","DOIUrl":"10.1002/nep3.70017","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 3","pages":"203-205"},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758567","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":"Effects of senescence on astrocyte to brain endothelial cell signaling.","authors":"Shuzhen Guo, Gen Hamanaka, Fang Zhang, Janice Lee, Ji Hyun Park, Wenlu Li, Ken Arai, Eng H Lo","doi":"10.1002/nep3.70013","DOIUrl":"10.1002/nep3.70013","url":null,"abstract":"<p><strong>Background: </strong>Aging affects almost all aspects of central nervous system (CNS) function, including the blood-brain barrier (BBB). Here, we use cell culture models to ask whether senescence, a cellular feature of aging, alters the BBB by modifying interactions between astrocytes and brain endothelial cells.</p><p><strong>Methods: </strong>Human astrocyte and Human brain microvascular endothelial cells were subcultured and maintained for cells at low and high passages, then confirmed with senescence-associated β-galactosidase staining and gene expression of cyclin-dependent kinase inhibitor 2A (<i>Cdkn2a</i>). After coculturing with astrocyte, the Alexa Fluor 488-labeled bovine serum albumin (Alexa 488-BSA) was used as a tracer to measure the permeability of brain endothelial cells; the expression of related proteins was measured by quantitative real-time polymerase chain reaction. Reducing the angiotensinogen (AGT) by small interfering RNA (siRNA) in senescent astrocyte to test the effect of angiotensin signals on endothelial permeability.</p><p><strong>Results: </strong>Young astrocytes (cumulative population doublings [CPD] ≤ 4) modified the expression of barrier genes and decreased brain endothelial permeability in coculture, whereas aged senescent astrocytes (CPD ≥ 9) had no effects (45.5% ± 18.0% vs. 122.8% ± 28.6%, <i>p</i> = 0.0016). Angiotensin is known to alter the BBB. Its precursor, AGT, is highly expressed in astrocytes in the brain. Therefore, we asked whether angiotensin signaling may mediate the loss of endothelial barrier-promoting properties in senescent astrocytes. Both protein and messenger RNA (mRNA) levels of AGT were increased in high-passage senescent astrocytes. Reducing AGT levels through siRNA restored the endothelial barrier-promoting effects of high-passage senescent astrocytes (<i>F</i> _(2,15) = 6.508, <i>p</i> = 0.0092). By contrast, brain endothelial cells at different passages did not change the expression of AGT in astrocytes.</p><p><strong>Conclusion: </strong>Taken together, these findings suggest that increased angiotensin signaling from astrocytes to brain endothelium may partly mediate the decrease of BBB function in the aging CNS.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 3","pages":"288-297"},"PeriodicalIF":4.1,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758548","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":"Acute hemichorea-hemiballism as the initial sign of cortical cerebral infarction: A case report.","authors":"Jin Xiong, Qian Yang, Yong Liu, Jianping Yu, Yili Wang, Lan Wen","doi":"10.1002/nep3.70014","DOIUrl":"10.1002/nep3.70014","url":null,"abstract":"<p><p>Hemichorea-hemiballism is classically associated with the contralateral basal ganglia, particularly involving the putamen and subthalamic nucleus, whereas cortical involvement remains a rare etiology. In this case, we present a patient with acute hemichorea-hemiballism secondary to multiple cortical infarcts demonstrated by neuroimaging. We review the literature to explore further significance of cortical-basal ganglia circuit dysfunction in movement disorders. This case highlights both the necessity of considering atypical infarction patterns in acute dyskinesia presentations and the importance of early imaging evaluation combined with targeted therapeutic interventions.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 4","pages":"396-400"},"PeriodicalIF":4.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890831","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":"Efficient analysis of toxicity and mechanisms of isoflurane on postoperative delirium by network toxicology and molecular docking.","authors":"Zhiming Dai, Qing Nan, Menglu Xu, Hongbao Li","doi":"10.1002/nep3.70015","DOIUrl":"10.1002/nep3.70015","url":null,"abstract":"<p><p>Postoperative delirium (POD), a prevalent neurological complication in older surgical patients, adversely affects recovery. Isoflurane, a common inhalational anesthetic, exhibits neurotoxic potential, but its role in POD pathogenesis remains unclear. Network toxicology and molecular docking strategies identified 38 shared targets between isoflurane (PubChem/ChEMBL) and POD (GeneCards). Protein-protein interaction networks (STRING/Cytoscape) screened eight core genes: catechol-O-methyltransferase (<i>COMT</i>), angiotensin l-converting enzyme (<i>ACE</i>), solute carrier family 6, member 3 (<i>SLC6A3</i>), cathepsin B (<i>CTSB</i>), apoptosis-related cysteine peptidase (<i>CASP3</i>), B-lymphoblastoma-2 gene (<i>BCL-2</i>), coagulation factor VII (<i>F7</i>), and nuclear receptor subfamily 3 (<i>NR3C1</i>). Functional enrichment (Gene Ontology [GO]/Kyoto Encyclopedia of Genes and Genomes [KEGG]) analyzed biological pathways. Key pathways implicated include calcium signaling, dopamine/catecholamine synaptic uptake, cholinergic synapses, endocrine resistance, and estrogen signaling. Molecular docking confirmed strong binding affinity between isoflurane and core targets (e.g., <i>CASP3</i>: affinity-5.54 kcal/mol), highlighting dopaminergic disruption and apoptotic activation. This study elucidates isoflurane's multi-target neurotoxicity in POD, providing a mechanistic foundation for mitigating postoperative neurological complications.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 4","pages":"386-395"},"PeriodicalIF":4.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890161","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":"The effects and mechanisms of stem cells and exosomes on neurological function protection and recovery after ischemic stroke.","authors":"Weihong Du, Yuxian He, Liangchen Li, Xinchun Jin, Panpan Geng","doi":"10.1002/nep3.70012","DOIUrl":"10.1002/nep3.70012","url":null,"abstract":"<p><p>Stroke can cause motor sensory impairment and cognitive impairment. Current interventions focus on thrombolysis or thrombectomy in the acute stage, and promoting the recovery of neurological function during the chronic stage. However, so far, the effect on ischemic brain injury has been limited. Many patients do not receive timely and effective treatment, resulting in high rates of disability and mortality worldwide. In recent years, basic studies have shown that stem cells and their exosomes have a good effect on the protection of nerve function in ischemic brain injury, which has attracted the attention of researchers. This review describes the progress of the work on the stem cells and exosomes in ischemic stroke, in particular, the promising therapy of exosomes.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 3","pages":"266-279"},"PeriodicalIF":4.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758593","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":"Targeting peripheral processes to protect the central nervous system.","authors":"Shen Li, Piotr Walczak, Xunming Ji, Johannes Boltze","doi":"10.1002/nep3.70010","DOIUrl":"10.1002/nep3.70010","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 2","pages":"117-119"},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746011","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":"Beta cells to brain cells: The pivotal role of insulin and glucose metabolism in Alzheimer's disease.","authors":"Stanley S Schwartz, Elizabeth M Rhea, William A Banks, Mary E Herman","doi":"10.1002/nep3.70008","DOIUrl":"10.1002/nep3.70008","url":null,"abstract":"<p><p>The risk factors and neuropathologies of cognitive decline and the onset and progression of dementia-related disorders were, until recently, obtuse. A critical predisposing factor to Alzheimer's disease (AD) that has emerged is glucose dysmetabolism. It is now understood that energy imbalances or excess nutrient intake sit in the crosshairs of neurodegeneration. Within the brain, the regulation of glucose operates semiautonomously from the periphery to ensure a defended, uninterrupted supply of glucose for neuronal processes. In this localized brain energetic milieu, hyperglycemia, hyperinsulinemia, and insulin resistance constitute independent risk factors for AD. Disturbances in the blood‒brain barrier (BBB) and brain insulin resistance are two newly understood insults connecting glucose metabolism with AD. This dysglycemia waylays insulin signaling, an otherwise potentially protective mechanism against AD plaques. In parallel, studies in the clinical setting demonstrate that glucose-lowering in patients with type 2 diabetes (T2D) reduces the risk of AD. The American Diabetes Association (ADA) elevated its guidelines to include cognitive issues (or risk) as a comorbidity in T2D patient treatment plans. Choice of antidiabetes therapy is imperative: evidence supports the use of metformin, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor analogs, and sodium glucose cotransporter 2 inhibitors to help prevent and mitigate cognitive outcomes and AD. Sulfonylureas, on the other hand, may actually worsen cognitive deficits and integrity. We are at a fascinating juncture: preclinical research is at a stage to inform the development of rational previously unexplored targets. Simultaneously, current clinical evidence is translatable now into real-world strategies to reduce the incidence and severity of comorbid AD in our aging population.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 2","pages":"145-164"},"PeriodicalIF":4.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745956","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":"A comprehensive review on adaptive plasticity and recovery mechanisms post-acquired brain injury.","authors":"Ravi Kumar Rajan","doi":"10.1002/nep3.70006","DOIUrl":"10.1002/nep3.70006","url":null,"abstract":"<p><p>Adaptive plasticity, the brain's ability to reorganize and form new neural connections after injury, is crucial for recovery following acquired brain injury (ABI). This process involves axonal sprouting, dendritic remodeling, and neurogenesis, which restore neural connections and compensate for lost functions. While neuroinflammation and reactive astrocytes aid tissue repair, optimizing these responses to minimize secondary damage remains a challenge. Brain-derived neurotrophic factor (BDNF) plays a vital role in neurogenesis and dendritic growth, positioning it as a potential therapeutic target for brain repair. Rehabilitation strategies that stimulate these adaptive changes can enhance neuroplasticity and functional recovery. The complexity of ABI recovery is influenced by factors such as injury severity, age, and genetic and epigenetic factors, which regulate neuronal repair and synaptic plasticity. Maladaptive plasticity refers to compensatory mechanisms that initially aid recovery but ultimately become harmful. Severe injuries like traumatic brain injury (TBI) and stroke can trigger adaptive responses, such as axonal sprouting, but excessive reliance on these processes may become maladaptive. In contrast, mild TBIs offer greater recovery potential. Age-related differences in plasticity complicate recovery, with younger individuals exhibiting greater plasticity and older adults experiencing reduced plasticity and increased likelihood of maladaptive changes. Genetic factors, such as <i>BDNF</i> gene polymorphisms and DNA methylation, influence recovery outcomes. Neuroinflammation plays a dual role: acute inflammation supports recovery, while chronic inflammation can exacerbate damage. Precision medicine, tailored to an individual's genetic and epigenetic profile, offers promising strategies to optimize recovery. Growth factors like BDNF and insulin-like growth factor 1 (IGF-1) are essential for neurogenesis, synaptic plasticity, and neural network reorganization, supporting both structural and functional recovery. However, maladaptive plasticity must be managed carefully for effective recovery. Targeted rehabilitation therapies, along with pharmacological agents and neuromodulation techniques, offer insights into personalized treatment strategies to enhance adaptive plasticity and optimize ABI recovery outcomes. This review explores the mechanisms of adaptive plasticity following ABI and discusses therapeutic interventions to support and optimize recovery, offering promising avenues for improving patient outcomes.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"3 3","pages":"226-252"},"PeriodicalIF":4.1,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758516","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}