Reviews in the Neurosciences最新文献

{"title":"Interpreting peripheral immune phenotypes in Parkinson's disease: an immune-context framework for biomarker qualification.","authors":"Osman Kahveci, Ulaş Ay, Hakan Gürvit","doi":"10.1515/revneuro-2026-0155","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0155","url":null,"abstract":"<p><p>Peripheral immune alterations are widely reported in Parkinson's disease (PD), but their biological meaning and clinical utility remain uncertain because circulating immune profiles are shaped by aging, latent infection, medication exposure, comorbidity, disease stage, and preanalytical conditions. This concept-driven narrative review examines how technically valid peripheral immune findings should be biologically interpreted and clinically qualified through an immune-context phenotyping framework. Available human evidence suggests alterations in neutrophil- and monocyte-related inflammatory indices and cellular states, α-synuclein-responsive T-cell pathways, cytotoxic and regulatory T-cell states, B-cell phenotypic alterations, and peripheral-central immune associations. Much of this evidence, however, derives from cross-sectional and cohort-dependent studies, and within the human evidence considered in this review, PD specificity remains insufficiently established for most candidate signals. An observed blood difference may reflect altered production, survival, differentiation, redistribution, denominator effects, systemic inflammatory context, or measurement-related distortion rather than a single disease mechanism. Immune-context phenotyping, therefore, integrates trait, state, disease-trajectory, measurement, and treatment contexts with biological identifiability, disease-control comparisons, cross-compartment corroboration, repeated sampling, and external validation. The framework adapts established biomarker concepts to distinguish diagnostic, prognostic, monitoring, predictive, pharmacodynamic/response, and treatment-selection claims without treating peripheral target engagement, CNS engagement, pathway modification, and clinical benefit as equivalent. Based on the human evidence considered in this review, no peripheral immune phenotype appears ready for stand-alone clinical implementation in PD. The proposed framework defines a testable path from descriptive peripheral immune associations toward biologically coherent, temporally informative, and clinically qualified phenotypes.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221139","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":"Monoamine receptors of intrinsic spinal neurons and their role in mammalian locomotor control: from physiology to pathology.","authors":"Mariya Mikhailova, Tatiana Vyunova, Yurii Sysoev, Andrey Butylin, Anna Sungurova, Pavel Musienko","doi":"10.1515/revneuro-2026-0121","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0121","url":null,"abstract":"<p><p>Locomotor impairment is one of the most devastating consequences of spinal cord injury (SCI) and cannot be adequately overcome by existing rehabilitation methods. Numerous studies in spinalized mammals have demonstrated that serotonin, dopamine, and noradrenaline receptors located on spinal cord cells below the injury level play an important role in locomotor recovery. Hence, these monoamine receptors (MARs) represent promising targets for pharmacological rehabilitation following SCI, but no drug targeting them has yet proven sufficiently effective for locomotor recovery or reached clinical use. This review summarizes current data on the spinal localization of MARs, their postinjury changes (expression and function), and the role of specific receptor subtypes and their combinations in regulating kinematic, kinetic, and electromyographic locomotor parameters in intact and spinalized mammals. Specifically, the studies reviewed here show that some MARs are important for locomotor control in healthy animals, while the role of others becomes apparent only after SCI. Data on changes in receptor expression following SCI are contradictory and strongly depend on the experimental protocol, animal species, and sex, as well as on the type of sample analyzed. Finally, targeting different receptor subtypes affects distinct locomotor parameters, whereas simultaneous targeting of multiple receptors (e.g., 5-HT1AR + 5-HT2A/2CR + D1R + α2AR) can produce a synergistic effect. Therefore, the development of highly selective drugs and knowledge of post-traumatic changes occurring in receptors will enable targeting of a narrow spectrum of receptors and correction of individual locomotor parameters depending on the degree of their impairment.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149405","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":"Microglial lipid metabolism in perioperative neurocognitive risk: aging-related priming, organelle crosstalk, and lipid-redox injury.","authors":"Dingliang Cai, Xinlong Ke, Fangla Luo, Yijing Li, Huajing Cai, Jihong Zhu, Yeru Chen, Gang Chen","doi":"10.1515/revneuro-2026-0136","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0136","url":null,"abstract":"<p><p>Perioperative neurocognitive disorders (PND) are clinically important complications in older surgical patients, but broad neuroinflammatory models do not fully explain age-related susceptibility or failed recovery. Aging alters microglial surveillance, phagocytosis, mitochondrial function, lipid handling, and inflammatory thresholds before surgery. This mechanism-focused narrative review, informed by a structured literature search, examines impaired microglial lipid handling as an interface between brain aging and perioperative cognitive vulnerability. Evidence is organized along three axes: lipid sensing, uptake, and storage; lipid catabolism and polyunsaturated fatty acid (PUFA) remodeling; and lipid-redox injury with downstream synaptic and circuit dysfunction. Direct perioperative support is strongest for age-associated microglial activation, immune modulation through triggering receptor expressed on myeloid cells 2 (TREM2), fatty acid desaturase 1 (FADS1)-dependent lipid remodeling, and neuronal or astrocytic ferroptosis-related injury. In contrast, microglial lipid catabolism mediated by multifunctional enzyme type 2 (MFE-2), apolipoprotein E4 (APOE4)-associated triglyceride metabolism, and TREM2-dependent lipid-droplet regulation are supported mainly by aging, neurodegeneration, or ischemic injury studies. Separating clinical and preclinical perioperative findings from nonperioperative mechanisms defines a testable lipid-neuroimmune framework for causal experiments, biomarker development, and mechanism-guided intervention.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128349","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":"Non-invasive neuromodulation in Alzheimer's disease: toward brain-heart coupling as a candidate framework for biomarker-guided adaptive intervention.","authors":"Weiran Zheng, Yuyu Ma, Chi Su, Zhiying Qiu, Ziyi Yan, Guizhi Xu, Duyan Geng, Alan Wang","doi":"10.1515/revneuro-2026-0134","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0134","url":null,"abstract":"<p><p>Alzheimer's disease (AD) has entered an era of biologically informed, disease-modifying therapy, yet durable clinical benefit remains limited, highlighting the need for complementary interventions. Noninvasive neuromodulation has emerged as a promising strategy, but the field is still largely organized by device categories, stimulation targets, and short-term cognitive outcomes. This framing alone does not readily account for the marked heterogeneity, stage dependence, and limited durability reported across studies. This narrative review synthesizes clinical, preclinical, and mechanistic evidence across repetitive transcranial magnetic stimulation, transcranial electrical stimulation, sensory gamma entrainment, focused ultrasound, photobiomodulation, and transcutaneous vagus nerve stimulation. We propose that device classification is a useful starting point but an incomplete explanatory framework, because different modalities have been linked, with varying levels of evidence, to overlapping processes involving network reconfiguration, autonomic regulation, neurovascular function, inflammatory signaling, and clearance-related biology. Against this background, we examine the brain-heart axis and the central autonomic network (CAN) as a candidate intermediate level at which central neural and peripheral physiological responses to stimulation might be jointly characterized. Building on this view, we propose a biomarker hierarchy that extends from heart rate variability to directional and time-varying brain-heart coupling measures, which could be tested as candidate markers of physiological state, target engagement, and treatment responsiveness. At present, however, there is no prospective evidence that brain-heart coupling causally mediates the therapeutic effects of neuromodulation in AD. We, therefore, present brain-heart coupling as a testable candidate framework for studying state dependence, target engagement, and, ultimately, biomarker-guided adaptive neuromodulation.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117384","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":"A review on diffusion tensor imaging-based comprehensive intelligent diagnosis of Alzheimer's disease.","authors":"Hengfei Jia, Shuicai Wu, Xinnan Xue, Zongyang Li, Luyu Li, Huijing He, Qi Wang, Hongjian Gao, Caiyun Wen","doi":"10.1515/revneuro-2026-0088","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0088","url":null,"abstract":"<p><p>AI-assisted early diagnosis of Alzheimer's disease (AD) has substantial clinical value, and diffusion tensor imaging (DTI), which captures white matter microstructural alterations, has considerable potential across the AD continuum. However, major barriers to clinical translation remain. This review systematically evaluated the evolution of algorithmic paradigms, the effectiveness of multimodal fusion, and barriers to clinical generalization in DTI-based AD diagnosis. Using an \"Input-Model-Fusion\" evaluation framework, we analyzed 98 studies published from 2010 to 2026 and compared sample size, diagnostic task, validation design, and methodological quality. Four findings emerged. 1) Modality selection should be task-driven; single-modality DTI and multimodal fusion have different applicability across diagnostic tasks. 2) Algorithm choice was closely related to sample size: conventional machine learning, particularly support vector machines, predominated in small-sample studies, whereas deep learning architectures, including convolutional neural networks, graph convolutional networks, and Transformers, were more widely used with large datasets. 3) Substantial performance degradation in multicenter or external validation highlighted persistent limitations in clinical generalizability. Data source, sample representativeness, feature processing, validation strategy, acquisition protocol, and software pipeline heterogeneity remain important constraints on clinical translation and cross-study comparability of DTI metrics. 4) Hippocampal pathways, the corpus callosum, fornix, and cingulum showed relatively stable discriminative value. Future research should move beyond \"algorithm accuracy competition\" toward clinical pragmatism by prioritizing task alignment, standardized DTI acquisition and processing, external validation, and neurobiological interpretability.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117390","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":"Central nervous system involvement of hantaviruses: clinical presentations, neuroimaging findings, and current implications.","authors":"Koyar Hiwa Raouf, Zahra Kazemaini, Mehrafarin Ataei, Hesan Abbasi, Arash Esmaeili, Ghazaleh Baghaei-Shiva, Artin Darbezin Zanjan, Zahra Hosseinpour Dahka, Amirreza Jabbaripour Sarmadian, Diba Lotfi, Shaghayegh Mohammadioun, Mohammad Pourashory, Mohammadreza Saleh, Tara Shahmoradi, Mahsa Zargaran, Mahsa Hosseini Kakroudi, Zohreh Meskar, Kiarash Saleki, Nima Rezaei","doi":"10.1515/revneuro-2026-0104","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0104","url":null,"abstract":"<p><p>Because of their involvement in outbreaks, hantaviruses as emerging zoonotic diseases have been regarded a public health issue. Recent reports have identified CNS symptoms of hantavirus infection, although the data are still relatively sparse and inconsistent, especially for <i>Andes orthohantavirus</i> (ANDV) and to a lesser extent Puumala virus (PUUV). Reported neurological features include headache, dizziness, altered mental state, seizures, focal deficits, and peripheral neuropathy, possibly accompanied by ocular symptoms such as impaired vision and photophobia. The results of neuroimaging have been inconsistent and nonspecific, ranging from hemorrhagic or edematous changes to thalamic or brainstem abnormalities and splenial lesions. Evidence could suggest that endothelial dysfunction, capillary leak, inflammatory damage, and, in certain situations, potential intrathecal immunological responses or direct viral presence may all contribute to CNS involvement. However, most evidence stems from case reports or case series, and causative neuroinvasion may not have been fully demonstrated. Recent studies, especially the recent ANDV-associated outbreak, may emphasize the necessity for rigorous neurological examination. A better understanding of the neurological range of hantavirus infection may enhance detection, risk stratification, and supportive therapy.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907794","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":"Periodic EEG: clinical settings, <i>in vitro</i> models, and potential mechanisms.","authors":"Roger D Traub, Andreas Draguhn","doi":"10.1515/revneuro-2026-0087","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0087","url":null,"abstract":"<p><p>Periodic complexes occur in the electroencephalogram (EEG) during a number of pathological conditions, often having a poor prognosis (Kuroiwa and Celesia 1980). The contexts in which periodic EEGs occur generally fall into three major categories: infections, sequelae to hypoxic/ischemic events, and metabolic disorders. In this review, we examine morphological and electrophysiological data from <i>in vitro</i> preparations. These data suggest several cellular mechanisms, which may underlie periodic EEGs, including altered excitation-inhibition relations, tonic activation of metabotropic glutamate receptors, altered neuromodulation, and electrical coupling of neurons by cell fusion or gap junctions. Some of the proposed mechanisms are empirically testable: for example, the occurrence of very fast oscillations (>∼70 Hz) superimposed on periodic complexes, and the occurrence of gamma oscillations (∼30 Hz-∼70 Hz) between complexes. The <i>in vitro</i> data further suggest an hypothesis concerning why some patients with periodic EEGs respond to anticonvulsant drugs (ACDs), while other patients do not: if the main cellular mechanism for neuronal synchrony involves excitatory chemical synapses, then a response to ACDs is possible; however, if a major factor in neuronal synchrony involves electrical coupling - as can occur with viral infections - then a response to ACDs would not be expected.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892826","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":"BDNF-related brain-liver communication in metabolic syndrome: implications for anxiety and depression.","authors":"Chang Liu, Chen Sun, Chengxia Kan, Xiaodong Sun, Liang Zhu","doi":"10.1515/revneuro-2026-0110","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0110","url":null,"abstract":"<p><p>Metabolic syndrome is frequently accompanied by anxiety and depression, suggesting interactions between metabolic dysfunction and affective regulation. Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin receptor kinase B (TrkB) are involved in energy balance, neuroplasticity, stress adaptation, and emotional processing, positioning BDNF-related signaling as a potential interface within brain-liver communication. Experimental evidence strongly supports central BDNF-TrkB signaling in the regulation of feeding and energy expenditure, while central BDNF-sensitive pathways can also influence hepatic glucose production. Conversely, obesity and metabolic dysfunction alter the systemic lipid, endocrine, inflammatory, vascular, and neural environment, which can impair hypothalamic and hippocampal BDNF-related signaling. These processes occur within a broader neuro-metabolic network involving the liver, adipose tissue, gut, skeletal muscle, immune system, and vasculature rather than through a liver-specific pathway. Chronic stress, anxiety, and depression further intersect with metabolic dysfunction through partly distinct neuroendocrine and neuroplastic mechanisms, including hypothalamic-pituitary-adrenal axis and glucocorticoid signaling. Glucagon-like peptide-1 signaling represents an additional interface between metabolic regulation and central neuroplasticity, although the contribution of BDNF to its hepatic and neurobehavioral effects remains incompletely defined. Key uncertainties include the functional significance of liver-associated and circulating BDNF, BDNF-defined autonomic pathways to the liver, genetic variation, and tissue-specific therapeutic targeting. Future studies integrating circuit- and tissue-specific manipulation, standardized BDNF measurements, both sexes, and longitudinal human phenotyping are needed to distinguish causal mechanisms from associative relationships.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820013","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":"Noncoding RNAs in epilepsy: from molecular mechanisms to clinical translation.","authors":"Jing Wang, Xiaoge Hu, Mei Zheng, Ruotong Qin, Wanlin Zhao, Wei Jiang, Dongrui Ma","doi":"10.1515/revneuro-2026-0098","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0098","url":null,"abstract":"<p><p>Epilepsy comprises a heterogeneous group of brain disorders in which recurrent seizures arise from dynamic interactions among neuronal hyperexcitability, glial activation, neuroinflammation, vascular dysfunction, and maladaptive circuit remodeling. Despite advances in genetics, neuroimaging, and molecular profiling, clinically useful biomarkers remain limited, and disease-modifying therapies are still lacking. Noncoding RNAs (ncRNAs) have emerged as an important regulatory layer in epilepsy biology. MicroRNAs, long noncoding RNAs, circular RNAs, transfer RNA fragments, and other ncRNA species influence epileptogenesis through post-transcriptional repression, chromatin-associated regulation, competing endogenous RNA networks, stress-responsive translational control, and extracellular vesicle-mediated intercellular communication. These mechanisms converge on central pathological processes, including neuroinflammation, synaptic and ion-channel remodeling, neuronal injury, aberrant neurogenesis, blood-brain barrier dysfunction, and antiseizure drug resistance. Beyond brain tissue, circulating ncRNAs detectable in plasma, serum, cerebrospinal fluid, and extracellular vesicles have attracted increasing interest as minimally invasive biomarkers. Their relative stability in biofluids and potential ability to reflect disease-relevant cell-to-cell signaling support their translational relevance. However, clinical translation remains limited by substantial interstudy heterogeneity related to epilepsy subtype, sampling window, biospecimen handling, RNA isolation method, profiling platform, and normalization strategy. Preclinical studies targeting selected ncRNAs, particularly microRNAs, further support the possibility of RNA-based disease modification, although major challenges remain in target prioritization, CNS-directed delivery, and long-term safety. This Review integrates current knowledge of ncRNA biology in epilepsy with emerging biomarker and therapeutic evidence and outlines key steps required for clinical translation.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820087","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":"Glymphatic-meningeal lymphatic dysfunction drives remote organ injury after aneurysmal subarachnoid hemorrhage: a unified neuroimmune framework and time-stratified therapeutic roadmap.","authors":"Ying Dai, Jinshan Tie, Dan Zhu, Zhengchao Lv, Wei Wan, Haolun Chen, Wei Li, Chen Yu","doi":"10.1515/revneuro-2026-0129","DOIUrl":"https://doi.org/10.1515/revneuro-2026-0129","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH) confers substantial mortality and morbidity driven not only by primary brain injury but also by systemic remote organ complications across the pulmonary, cardiac, renal and gastrointestinal systems. Despite growing recognition of neuroimmune crosstalk in this process, a cohesive, systems-level model connecting intracranial hemorrhage to multi-organ dysfunction remains absent from the literature. Here, we propose a unified neuroimmune framework centered on a long-underappreciated mechanism: glymphatic and meningeal lymphatic drainage dysfunction is hypothesized to act as the upstream initiating event that forces brain-derived damage-associated molecular patterns, inflammatory cytokines and activated immune cells to spill into the systemic circulation. We systematically map three mechanistically distinct, mutually amplifying transmission pathways: the classical neuroendocrine-immune axis, the recently identified meningeal lymphatic-deep cervical lymph node immune drainage axis, and circulating humoral effectors exemplified by neutrophil extracellular traps. Most notably, we integrate these pathways with a temporally stratified immune continuum spanning early hyperinflammatory SIRS, stroke-induced immunodepression, and chronic low-grade inflammation - an integrative temporal architecture that has eluded prior single-organ or single-pathway studies. Grounded in this framework, we put forward a tiered, phase-specific neuroimmunomodulatory strategy that simultaneously addresses central inflammatory origins, systemic signal propagation, and end-organ tissue damage. By reframing remote organ injury as a time-dependent immune process rather than a collection of isolated organ complications, this work provides a mechanistic and translational roadmap for time-stratified clinical trials and redefines the investigative direction for multi-organ management in aSAH.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674528","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}