Reviews in the Neurosciences最新文献

{"title":"The glymphatic system and hydrocephalus: emerging insights into pathophysiological mechanisms.","authors":"Ziang Geng, Zeyi Yang, Pengtao Li, Ying Mao, Junji Wei","doi":"10.1515/revneuro-2026-0033","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0033","url":null,"abstract":"<p><p>Hydrocephalus is a complex neurological disorder traditionally thought to result from excessive cerebrospinal fluid (CSF) production, obstruction of CSF outflow, or impaired absorption. However, these classical theories have limitations in explaining key phenomena observed in certain clinical subtypes, such as normal pressure hydrocephalus. Recent advances in neuro-fluid dynamics have introduced the concept of the glymphatic system, a functional network in the brain that facilitates the exchange of CSF and interstitial fluid (ISF) along perivascular pathways and mediates the clearance of metabolic waste. This new perspective offers a fresh lens for understanding CSF circulation and fluid homeostasis. This review aims to reexamine the pathogenesis of hydrocephalus from the perspective of glymphatic dysfunction and, by integrating anatomical, physiological, and imaging evidence, explore its theoretical implications and clinical relevance.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-driven mechanisms in idiopathic intracranial hypertension: a critical synthesis.","authors":"Berrak Yetimler, Erdem Tüzün","doi":"10.1515/revneuro-2025-0148","DOIUrl":"https://doi.org/10.1515/revneuro-2025-0148","url":null,"abstract":"<p><p>Idiopathic intracranial hypertension (IIH) is increasingly recognised as a complex disorder characterized by elevated intracranial pressure (ICP), with evidence suggesting contributions from dysregulated cerebrospinal fluid (CSF) dynamics as well as metabolic, endocrine, and neurovascular mechanisms. IIH predominantly affects women of reproductive age who are living with obesity. Clinically, IIH may be asymptomatic or present with severe headaches, visual disturbances, and papilledema, with a risk of visual impairment in some untreated or refractory cases. Although the etiopathogenesis of IIH remains unclear, emerging evidence from metabolic and immunological studies suggests that immune-mediated mechanisms may contribute to disease pathophysiology. In this review, we synthesize current literature on the potential contribution of the immune system to IIH, integrating findings across obesity-associated inflammation, circulating cytokine profiles, comorbid inflammatory and autoimmune conditions, and markers of neuroglial stress and injury. We summarize converging data suggesting that IIH may, at least in part, be influenced by a pro-inflammatory milieu that affects CSF dynamics. While available studies highlight intriguing immunological signals, the underlying mechanistic pathways remain poorly resolved. Larger, longitudinal, and mechanistically grounded investigations are needed to clarify causality, identify relevant immune subtypes, and determine whether immune modulation may offer therapeutic opportunities in IIH.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin in T2DM: neurocognitive mechanisms and precision pharmacotherapy.","authors":"ZeZhong Tang, PeiHeng Li, XiZhou Huang, QianFa Long, Jinyun Niu, SongNa Yin, MingJun Hu","doi":"10.1515/revneuro-2026-0013","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0013","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that significantly predisposes individuals to delirium and dementia through multifaceted neurobiological pathways. The essence of this neurocognitive decline involves mechanisms such as central insulin resistance, chronic low-grade inflammation, and mitochondrial dysfunction. While metformin remains the cornerstone of T2DM management, its impact on the central nervous system exhibits a \"double-edged sword\" nature, balancing intrinsic neuroprotective properties against the potential neurotoxicity associated with vitamin B12 deficiency. This review aims to systematically synthesize epidemiological and clinical evidence linking metformin to neurocognitive outcomes, contrasting its efficacy with newer glucose-lowering agents such as GLP-1 receptor agonists and SGLT2 inhibitors. In addition, it sheds light on the reciprocal connectivity between systemic metabolic regulation and direct CNS modulation, specifically elucidating AMPK activation, the autophagy-lysosome axis, and the gut-brain and liver-brain axes. We review these molecular mechanisms to delineate the delicate trade-off between neuroprotection and risk, providing a framework for precision pharmacotherapy and biomarker-guided stratification in high-risk T2DM populations.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis as a central pathological axis in neurodegenerative diseases.","authors":"Ting Cheng, Mingwei Li, Yulong Yang, Zhihong Rao, Wenming Yang","doi":"10.1515/revneuro-2026-0037","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0037","url":null,"abstract":"<p><p>Glycolysis is increasingly recognized as a pathological backbone in neurodegenerative diseases rather than merely an accompanying epiphenomenon. This article first delineates the division of metabolic labor among neurons, astrocytes, microglia, and oligodendrocytes in the brain, with particular emphasis on cell type-specific glycolytic flux, lactate shuttling, and an integrated brain-periphery framework of energy metabolism. It then systematically compares alterations in glucose uptake, glycolytic intermediates, and lactate metabolism across Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Wilson disease (WD), Huntington's disease (HD), and multiple sclerosis (MS), highlighting pronounced heterogeneity across cell types, disease stages, and brain regions. These metabolic disturbances encompass not only global cerebral hypometabolism and an energy crisis, but also compensatory hyperglycolysis and inflammation-associated metabolic reprogramming in astrocytes and microglia, and extend further to systemic metabolic phenotypes involving peripheral blood cells, muscle, and liver. The article summarizes recent methodological advances for characterizing glycolytic reprogramming, including fluorodeoxyglucose positron emission tomography (FDG-PET), hyperpolarized carbon-13 magnetic resonance spectroscopy(ˆ13C-MRS), metabolomics, single-cell and spatial transcriptomics, genetically encoded metabolic sensors, and Seahorse assays. In addition, potential therapeutic strategies are discussed, focusing on targets such as 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3), the astrocyte-neuron lactate shuttle (ANLS), microglial glycolysis and lactylation, as well as systemic metabolic modulation and nanodelivery approaches. Finally, key challenges are highlighted, including unclear causal relationships, biphasic and cell type-specific effects, insufficient brain-periphery integration, and the lack of standardized metrics, underscoring the need for longitudinal, multimodal, and stage-specific strategies to reposition glycolysis as a targetable therapeutic dimension in neurodegenerative diseases.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From peripheral neurotoxicity to central dysfunction: linking neuropathic pain and cognition in chemotherapy-induced peripheral neuropathy.","authors":"Laura Cherchi, Antonio Giuliano Zippo, Lisa Fantoni, Valentina Alda Carozzi, Paola Marmiroli","doi":"10.1515/revneuro-2025-0146","DOIUrl":"https://doi.org/10.1515/revneuro-2025-0146","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neurotoxicity (CIPN) represents a significant clinical burden, affecting 70-80 % of patients during treatment and persisting chronically in 20-30 % of survivors. While peripheral nerve injury is the primary pathological hallmark, emerging evidence demonstrates that central nervous system (CNS) dysregulation plays a crucial role in pain chronification and associated cognitive impairment. This review synthesizes recent findings on cortical and subcortical alterations that drive neuropathic pain processing in CIPN, examining dysregulated glutamatergic and GABAergic neurotransmission, altered voltage-gated ion channel expression, and central sensitization across key pain-modulatory brain regions including the prefrontal cortex, anterior cingulate cortex, somatosensory cortices, and periaqueductal gray. We address chemotherapy-induced cognitive impairment (\"chemobrain\") as a manifestation of shared neuroinflammatory mechanisms linking peripheral nerve injury to CNS pathology. In fact, peripheral neuropathy-triggered neuroinflammation, characterized by microglial activation and cytokine dysregulation, compromises the blood-brain barrier and impairs hippocampal-dependent memory, synaptic plasticity, and adult neurogenesis. The paper integrates findings from both animal models and human patients and discusses how animal models of CIPN reveal central nervous system engagement beyond peripheral pathology. This review emphasizes CIPN as a disorder profoundly affecting central pain modulation and cognition, requiring integrated therapeutic strategies addressing both peripheral and central nervous system pathology.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbiota-gut-brain axis as a driver of secondary brain injury after aneurysmal subarachnoid hemorrhage: from bidirectional vicious cycle to therapeutic opportunities.","authors":"Chunfeng Li, Wei Wan, Chong Li, Dan Zhu, Jipin Li, Sili Yang, Wenzi Chen, Haolun Chen, Chen Yu","doi":"10.1515/revneuro-2026-0040","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0040","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating stroke subtype with high morbidity and mortality, significantly contributed to by secondary brain injuries such as early brain injury and delayed cerebral ischemia. Despite advances in acute management, effective neuroprotective strategies remain an unmet need. The microbiota-gut-brain axis (MGBA), a pivotal bidirectional communication network, has recently emerged as a critical modulator of pathophysiology in acute brain injuries. However, its precise role and therapeutic potential in aSAH are not systematically defined. This review synthesizes clinical and preclinical evidence to move beyond correlation and delineate the spatiotemporal dynamics and the mechanisms that may underlie of MGBA dysregulation post-aSAH. We conceptualize a self-amplifying \"brain-gut-brain\" vicious cycle: the initial brain injury may disrupt intestinal barrier integrity and microbiota ecology via neuroendocrine and inflammatory pathways; in turn, gut-derived signals (e.g., altered microbial metabolites, endotoxin translocation) may propagate systemic inflammation and exacerbate neuroinflammation, blood-brain barrier disruption, and cerebral ischemia. We dissect this cycle by detailing the key molecular bridges (tryptophan metabolites, short-chain fatty acids, bile acids), signaling pathways (e.g., TLR4/NF-κB, NLRP3 inflammasome), and central effectors involved. Furthermore, we provide a critical, stratified evaluation of MGBA-targeting therapeutic strategies - including probiotics, prebiotics, fecal microbiota transplantation, and metabolite supplementation - assessing their mechanistic rationale, level of evidence, and translational challenges. Finally, we outline future directions emphasizing the need for defining therapeutic windows, establishing causal proof, and integrating MGBA modulation into multimodal neurocritical care. Harnessing the MGBA presents a novel and promising paradigm for developing adjunctive neuroprotective therapies to improve outcomes after aSAH.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoxetine reprograms hippocampal mitochondrial subcellular proteomes in chronically socially isolated rats.","authors":"Snežana B Pajović, Dragana Filipović","doi":"10.1515/revneuro-2025-0152","DOIUrl":"https://doi.org/10.1515/revneuro-2025-0152","url":null,"abstract":"<p><p>Brain mitochondrial dysfunction may play a crucial role in the mechanisms of major depressive disorders, impairing neuronal bioenergetics and synaptic transmission. While the antidepressant fluoxetine (Flx) is primarily known for modulating serotonin levels, it may also enhance mitochondrial function in stress-affected brain regions, particularly the hippocampus. This review summarizes findings from proteomic analyses of hippocampal nonsynaptic mitochondria (NSM) and synaptosomal mitochondria from adult male rats subjected to six weeks of chronic social isolation (CSIS), an animal model of depression, followed by Flx treatment lasting three weeks of six-week CSIS, compared to CSIS. In NSM of CSIS rats, Flx upregulates proteins involved in pyruvate metabolism, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and ATP synthesis, suggesting an overall enhancement of mitochondrial energy production. Additional upregulation encompasses one-carbon folate metabolism, mitochondrial transport, structural organization, and proteostasis. Within synaptosomal mitochondria, Flx induces a distinct yet complementary proteomic signature, upregulating selects TCA cycle enzymes and catalytic OXPHOS components, remodeling the respiratory chain to support enhanced bioenergetic capacity. Flx further upregulates proteins mediating ketone body and amino acid catabolism, antioxidant defense system and protein quality control mechanisms. Notably, monoamine oxidase-A exhibits consistent upregulation across both mitochondrial subpopulations, likely representing a compensatory response to maintain monoamine homeostasis. These findings suggest that Flx mediates part of its antidepressant effects through subcellular compartment-specific reprogramming of the mitochondrial proteome, underscoring mitochondria as one of the modulators of depression-related molecular alterations and potential therapeutic targets.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut-brain axis mediated therapeutic intervention to mitigate the epileptogenesis: insights from <i>Drosophila melanogaster</i>.","authors":"Manvitha Kadandelu, Sreelakshmi Periya, Punchappady Devasa Rekha, Shamprasad Varija Raghu","doi":"10.1515/revneuro-2025-0144","DOIUrl":"https://doi.org/10.1515/revneuro-2025-0144","url":null,"abstract":"<p><p>Drug-resistant epilepsy (DRE) is a prominent concern in the management of recurrent seizures. Anti-seizure medications (ASM), surgical intervention, and neurostimulation are a few classical remedial measures of epilepsy. Nevertheless, DRE requires immense investigation, a comprehensive understanding of holistic management, and additional therapeutic effects. Dysbiosis, an imbalance of the gut microbiome, is the foremost concern associated with various neurological disorders. In epilepsy, the gut microbiome plays a pivotal role in its pathophysiology, unveiling new avenues for microbiome-mediated strategies to treat epileptic patients. Furthermore, the differential gut microbial composition in epileptic patients serves as a cornerstone for advanced research to delineate the influence of each bacterial species on epilepsy. <i>Drosophila melanogaster</i>, a simple model organism with an evolutionarily conserved gut microbiome composition, can be efficiently deployed to scrutinize the role of discrete microbes and their influence on the gut-brain axis, impacting neurological disorders. In this review, the role of distinct bacterial species in influencing epileptic conditions and how model organisms like <i>Drosophila</i> can be employed to explore this realm are deliberated as a comprehensive overview.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular mechanisms of entorhinal cortex spontaneous and navigation-related grid cell oscillations.","authors":"Roger D Traub, Mark O Cunningham","doi":"10.1515/revneuro-2025-0145","DOIUrl":"10.1515/revneuro-2025-0145","url":null,"abstract":"<p><p>Intracellular recordings of grid cells have been previously obtained from principal neurons in the superficial medial entorhinal cortex (MEC) of behaving head-fixed mice. These recordings indicate that action potentials occur on the depolarizing phases of intracellular slow oscillations. Here we use network simulations and <i>in vitro</i> experiments to investigate the hypothesis that slow grid cell oscillations <i>in vivo</i> have cellular mechanisms similar to those of spontaneous slow wave oscillations (SWO) in drug-free entorhinal cortex (EC) slices. Simulations suggest that electrical coupling plays a vital role in oscillation genesis; slice experiments demonstrating spikelets in entorhinal cortex SWO are consistent. We reviewed previously published (by others) <i>in vivo</i> grid cell recordings and found spikelets to be present in entorhinal principal neurons. The data suggest that afferent inputs to entorhinal cortex during exploration influence the period and phase of grid cell oscillations, but may not be necessary for the oscillations themselves; while both chemical and electrical synaptic coupling <i>within</i> the entorhinal cortex give the oscillation its special characteristics. Importantly, spikelets are not only interesting in themselves, but imply the existence of pyramidal cell electrical coupling which may help to create local modules of grid cells having similar periods, spatial phases, and orientation.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology of the kynurenine pathway and its implications in CNS disorders.","authors":"Qi Zhang, Yu-Hui Tang, Xiao-Qing Tang","doi":"10.1515/revneuro-2025-0130","DOIUrl":"10.1515/revneuro-2025-0130","url":null,"abstract":"<p><p>The kynurenine pathway (KP), a crucial route of tryptophan (TRP) catabolism, has emerged as a focal point of investigation because of its complex involvement in regulating central nervous system (CNS) function. This metabolic pathway, which operates in various cell types within the CNS, closely links immune responses, neurotransmission, and neuroinflammation. This review provides an in-depth exploration of the KP, delineating its enzymatic constituents, metabolite profiles, and multifarious roles in sustaining CNS homeostasis, with potential implications for neuropathological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder (MDD), and schizophrenia (SCZ). In addition to the roles of the KP in the pathogenesis of the abovementioned diseases, the related advancements in treatment are discussed.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}