Alisha Aroor, Zahra Sadri, Nicole Pinzón-Hoyos, Nicole D Schartz, Amy L Brewster
{"title":"Temporal profiling of hippocampal astrocyte reactivity reveals persistent GFAP cleavage and complement C3 association after status epilepticus.","authors":"Alisha Aroor, Zahra Sadri, Nicole Pinzón-Hoyos, Nicole D Schartz, Amy L Brewster","doi":"10.1007/s00429-026-03175-9","DOIUrl":"10.1007/s00429-026-03175-9","url":null,"abstract":"<p><p>Astrocytes play essential roles in maintaining brain homeostasis, regulating synaptic transmission, supporting neuronal metabolism, and preserving blood-brain barrier integrity. Following prolonged seizures, such as status epilepticus (SE), astrocytes undergo structural and molecular changes that may contribute to epileptogenesis. Although reactive astrogliosis after SE is well documented, the temporal dynamics of astrocytic cytoskeletal remodeling and its relationship to complement activation remain incompletely defined. Using a pilocarpine-induced SE rat model, we examined hippocampal astrocyte responses at multiple time points (4 h, 1 day, 3 days, and 1-, 2-, 3-, or 5-weeks post-SE). Glial fibrillary acidic protein (GFAP) distribution was assessed by immunohistochemistry (IHC), and total GFAP protein levels and cleavage were quantified by western blotting (WB). We further evaluated the cellular association between GFAP-positive astrocytes and complement component C3 by immunofluorescence (IF). IHC revealed progressive astrocytic hypertrophy and increased GFAP immunoreactivity in the CA1 region, peaking at 2-3 weeks post-SE and modestly declining by 5 weeks. In contrast, WB demonstrated sustained elevations in total GFAP protein from 2 to 5 weeks post-SE, accompanied by significant accumulation of GFAP cleavage fragments. Quantitative analysis of GFAP breakdown products revealed progressive proteolytic processing during the latent-to-chronic phases of epileptogenesis. IF showed robust colocalization of C3 within hypertrophic GFAP-positive astrocytes at 2-3 weeks post-SE. When integrated with our prior mapping of microglial activation and complement dynamics, these findings indicate that astrocytic GFAP upregulation and cleavage follow early microglial activation and parallel sustained complement C3 expression. Together, our results demonstrate that SE induces dynamic and persistent astrocytic cytoskeletal remodeling characterized by coordinated GFAP synthesis and proteolysis, along with complement association. These findings highlight GFAP cleavage as a potential marker of astrocytic stress post-SE and support a temporally integrated astroglial-complement response following SE.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Moscow Wada protocol: an optimised protocol for language and memory lateralization.","authors":"Irina Provlotskaya, Alina Minnigulova, Elizaveta Gordeyeva, Dmitry Marchak, Andrey Zuev, Nikita Pedyash, Olga Dragoy","doi":"10.1007/s00429-026-03147-z","DOIUrl":"10.1007/s00429-026-03147-z","url":null,"abstract":"<p><p>The Wada test is an invasive procedure used to assess language and memory lateralization. Despite the widespread use of the Wada test in the population of people with epilepsy, the two existing standardized protocols for conducting the procedure are methodologically different and do not fully account for language comprehension as a separate domain. In this study, we presented a novel, optimized Wada protocol developed and tested using Russian language stimuli, with an English adaptation provided to support crosslinguistic application. The protocol was applied to a cohort of eight patients undergoing presurgical evaluation, demonstrating consistent lateralization patterns: language comprehension was predominately bilateral, while production was unilaterally localized in most patients, and memory representation was either bilaterally and right-hemisphere organized. Postoperative outcomes available for four patients confirmed the protocol's ability to identify eloquent hemispheres, as patients with unilateral language dominance showed transient language deficits after surgery, whereas those with bilateral representation did not. Furthermore, the intraoperative mapping results also corroborate the obtained outcomes. These findings support the protocol's enhanced applicability for determining individual patterns of language and memory lateralization, offering valuable insights to improve presurgical planning and treatment strategy selection for epilepsy patients.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668415","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}
Giuseppina Bevacqua, Marco Ciavarro, Lorenzo Gaetani, Valentina Grespi, Carlo Conti
{"title":"Thalamocortical connectivity and nucleus-specific thalamic dysfunction in temporal lobe epilepsy: an integrative review.","authors":"Giuseppina Bevacqua, Marco Ciavarro, Lorenzo Gaetani, Valentina Grespi, Carlo Conti","doi":"10.1007/s00429-026-03169-7","DOIUrl":"10.1007/s00429-026-03169-7","url":null,"abstract":"<p><p>Temporal lobe epilepsy (TLE) is increasingly recognized as a distributed network disorder extending beyond mesial temporal structures. Among the brain regions implicated in epileptic network organization, the thalamus has emerged as a key hub due to its extensive structural and functional connections with cortical, limbic, and subcortical systems.This integrative review aimed to synthesize current evidence regarding nucleus-specific thalamic abnormalities and thalamocortical connectivity alterations in TLE.A literature search was conducted following PRISMA guidelines using PubMed and Google Scholar databases. Twenty-eight studies were included in the qualitative synthesis, with nineteen studies providing detailed nucleus-specific structural, functional, or electrophysiological characterization of thalamic involvement.Across structural MRI, diffusion imaging, resting-state functional MRI, magnetoencephalography, and stereo-electroencephalography studies, convergent evidence indicated preferential involvement of the anterior thalamic nucleus (ANT), mediodorsal nucleus (MD), pulvinar, and intralaminar nuclei. TLE with mesial temporal sclerosis generally exhibited more extensive thalamic atrophy and thalamotemporal disconnection, whereas MRI-negative TLE showed more heterogeneous functional and network-level abnormalities. Electrophysiological studies demonstrated dynamic thalamic participation in seizure propagation and network synchronization, supporting an active role of thalamic nuclei in epileptic processes. Emerging longitudinal evidence further suggests that thalamocortical networks may undergo postoperative reorganization following successful epilepsy surgery.Overall, the available evidence supports a transition from a predominantly hippocampocentric framework toward a distributed thalamocortical network model of TLE. Nucleus-specific thalamic dysfunction appears to contribute to seizure propagation, cognitive impairment, and large-scale network dysregulation, highlighting the importance of multimodal approaches for understanding epileptic network organization.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Environmental enrichment modulates parvalbumin interneuron deficits and plasticity-related signaling after early postnatal NMDA receptor hypofunction in male rat visual cortex.","authors":"Ane Murueta-Goyena, Naiara Ortuzar, Susana Bulnes, José Vicente Lafuente, Harkaitz Bengoetxea","doi":"10.1007/s00429-026-03168-8","DOIUrl":"10.1007/s00429-026-03168-8","url":null,"abstract":"<p><p>Sensory processing deficits in schizophrenia have been linked to dysfunction of cortical inhibitory interneurons, particularly parvalbumin-expressing (PV+) populations. NMDA receptor hypofunction during development is known to disrupt interneuron maturation, but its long-term impact on visual cortex circuitry and the potential for experience-dependent modulation in adulthood remain unclear. Here, we examined the effects of early postnatal N-methyl-D-aspartate (NMDA) receptor blockade with MK-801 on the number of PV+ and somatostatin-expressing (SST+) interneurons in the primary visual cortex (V1) and assessed whether environmental enrichment (EE) in adulthood modulates these alterations by analyzing molecular changes using Western blot. Male Long-Evans rats received MK-801 (0.5 mg/kg) or saline from postnatal day 10-20, followed by EE exposure from P55-73. Stereological analyses revealed a marked reduction of PV-immunoreactive cells in layers II/III and IV, while SST+ populations were largely preserved. EE increased the number of PV-immunoreactive cells across groups, and modestly enhanced SST+ cells in layer IV, although no treatment × housing interaction was detected, indicating a general enrichment-related effect. At the molecular level, MK-801 reduced expression of the NMDA receptor subunit NR1 and increased Akt phosphorylation, whereas EE enhanced PSD95 expression, ERK phosphorylation, and GABA<sub>A</sub> β2/3 subunit levels, without increasing NR1 levels. These findings indicate that early NMDA receptor hypofunction induces long-lasting, subtype-specific alterations in inhibitory circuitry in V1. EE in adulthood engages molecular pathways associated with synaptic plasticity and modulates interneuron immunoreactivity, suggesting that inhibitory circuits retain some capacity for experience-dependent remodeling despite persistent receptor-level deficits.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Psychological and neurological benefits of physical activity: impact on mental health, Parkinson's disease, and Alzheimer's disease.","authors":"Gang Li, Yating Li","doi":"10.1007/s00429-026-03132-6","DOIUrl":"10.1007/s00429-026-03132-6","url":null,"abstract":"<p><p>This review synthesizes current evidence on the psychological and neurological benefits of physical activity, with emphasis on mental health, Parkinson's disease (PD), and Alzheimer's disease (AD). Physical inactivity is increasingly recognized as a modifiable risk factor that may exacerbate neuroinflammatory and metabolic dysfunctions associated with these conditions. Structured exercise has been shown to activate muscle-brain signaling pathways, including neurotrophic factors (BDNF, IGF-1, VEGF), immune modulation (IL-6, IL-10), metabolic regulators (PGC-1α, SIRT1), and peripheral mediators such as myokines and gut-brain axis components. For mental health, exercise is associated with reductions in depressive, anxiety, and stress-related symptoms, potentially through HPA-axis recalibration, neurotransmitter remodeling (serotonin, dopamine), and enhanced endocannabinoid signaling. These changes are supported by fMRI and EEG studies showing improved prefrontal-limbic connectivity and cognitive resilience. In PD, exercise interventions are linked to improvements in motor control, balance, and mood, likely mediated by dopaminergic integrity, neurotrophic support, and anti-inflammatory effects, with multimodal programs (aerobic, resistance, and dance-based) often demonstrating superior outcomes. In AD, mid-life physical activity has been associated with reduced dementia risk in epidemiological studies; proposed mechanisms include enhanced amyloid/tau clearance, glymphatic function, and synaptic adaptation, with some RCTs reporting hippocampal volume preservation and improved network connectivity. Shared mechanisms across conditions include neurotrophic upregulation and anti-inflammatory effects, whereas distinct pathways involve dopaminergic circuit remodeling in PD and glymphatic facilitation in AD. Clinical translation through FITT principles (frequency, intensity, time, type) requires personalized prescriptions, strong adherence strategies, and multidisciplinary integration. Despite methodological heterogeneity and limitations in the existing trials, structured physical activity emerges as a scalable, non-pharmacological intervention with potential for prevention, symptom management, and neuroprotection. Larger, well-designed studies are needed to optimize its application and clarify long-term disease-modifying effects.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668365","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":"Resting-state EEG connectome topology and social norm processing in healthy young adults.","authors":"Nicola Davide Cavallo, Simone Papallo, Marianna Chianese, Leandro Donisi, Chiara Baiano, Gabriella Santangelo, Luigi Trojano, Fabrizio Esposito","doi":"10.1007/s00429-026-03167-9","DOIUrl":"10.1007/s00429-026-03167-9","url":null,"abstract":"<p><p>Resting-state network topology may provide a powerful framework for understanding how large-scale brain organisation supports cognitive functions. However, the topological correlates of social cognition remain poorly characterised. This study examined whether individual differences in social cognition are associated with the global topology of the resting-state functional connectome derived from high-density EEG across canonical frequency bands. Twenty-eight healthy young adults underwent a comprehensive neuropsychological assessment, including measures of global cognition, theory of mind, empathy, and social norm processing. High-density eyes-closed resting EEG was acquired, and source-reconstructed connectivity matrices were estimated using the phase-locking value. For each frequency band, global graph-theoretical measures of segregation (average clustering coefficient, CC), integration (characteristic path length, CPL), and small-worldness were computed. We found selective associations between network topology and the intrapersonal component of social norm processing. Higher intrapersonal norm scores were related to lower CC and longer CPL, predominantly in the theta and alpha bands. These relationships held after controlling for demographic variables and were supported by multivariate analyses. No other social cognition measures showed equally significant associations with resting-state EEG topology. These findings suggest that individual variability in intrapersonal social norm processing may be associated with differences in the global organisation of the intrinsic functional connectome and highlight the relevance of investigating normative aspects of social cognition within a resting-state connectomics framework.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingbin Bian, Feihong Liu, Qian Wang, Han Zhang, Dinggang Shen
{"title":"Robust probabilistic measurement of structural-functional module consistency in infant brain development.","authors":"Lingbin Bian, Feihong Liu, Qian Wang, Han Zhang, Dinggang Shen","doi":"10.1007/s00429-026-03143-3","DOIUrl":"10.1007/s00429-026-03143-3","url":null,"abstract":"<p><p>Brain network is commonly divided into modules for analyzing their functionally segregated roles for group-level analysis in neuroimaging studies. Here, we introduce stochastic modules within brain networks for a robust probabilistic measurement of structural-functional module consistency (SFMC) in a group of subjects. Specifically, a stochastic module can be regarded as the chance of a brain region across subjects potentially being assigned to a group-level sub-network, characterized as an assignment probability for this brain region. This novel method has two advantages for evaluating inhomogeneous modules in brain networks. The first is that it can robustly evaluate the consistency between brain structural and functional modules whose population sizes are not necessary the same, and the second is that it is able to take into account the inter-individual variability of the modules for the groups. Moreover, compared with the conventional structural-functional coupling approach, our stochastic module-based method reveals a more pronounced decline in the coupling between structure and function, indicating stronger developmental reorganization. Our results using the dataset from Baby Connectome Project (BCP) show that the SFMC decreases from 0 to 5 years old, and is greater in primary brain regions, such as visual areas, while lower in more advanced cognitive regions, including those related to attention, control, and default mode network.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618424","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}
Blanca Sánchez-Moreno, Alicia Uceda-Heras, María de la Fuente-Fernández, Miguel Ángel García-Cabezas, Carmen Cavada, Javier Gilabert-Juan
{"title":"Comparative analysis of Foxp2 expression in the thalamus of mice, rats, and macaques: implications for the evolution of language circuits.","authors":"Blanca Sánchez-Moreno, Alicia Uceda-Heras, María de la Fuente-Fernández, Miguel Ángel García-Cabezas, Carmen Cavada, Javier Gilabert-Juan","doi":"10.1007/s00429-026-03165-x","DOIUrl":"10.1007/s00429-026-03165-x","url":null,"abstract":"<p><p>Foxp2 is a transcription factor essential for the development and function of neural circuits involved in language. Although its expression has been extensively characterized in the cortex and basal ganglia, its organization within the adult thalamus remains poorly understood. In this study, we present a comparative analysis of Foxp2 protein expression across thalamic nuclei in mice, rats, and macaques, with a focus on nuclei associated with higher-order cognitive functions and language-related circuits in humans. We found that Foxp2 is expressed in most thalamic nuclei across species, with a consistent absence in the reticular nucleus and zona incerta. Expression was highest in midline and intralaminar nuclei, whereas the anterior group showed low and variable expression among species. Macaques exhibited broader and, in some nuclei, more intense FoxP2 expression, particularly in associative regions such as the pulvinar and parts of the ventral group, consistent with differences in thalamocortical organization across species. This distribution suggests a conserved role for Foxp2 in shaping thalamic circuits supporting sensorimotor integration, attention, memory, and linguistic processing. Phylogenetic comparisons suggest that enhanced Foxp2 expression in associative thalamic territories in primates may be related to the increased complexity of thalamocortical circuits. These findings provide molecular and anatomical insights into the organization of thalamocortical networks and may offer a framework for understanding their involvement in higher-order cognitive functions and neuropsychiatric disorders.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molly E Klug, Mugil V Shanmugam, Haoyang Huang, Don Arnold, Joel D Hahn, Scott E Kanoski
{"title":"Transsynaptic neural circuit mapping of ventral hippocampus motivational control systems.","authors":"Molly E Klug, Mugil V Shanmugam, Haoyang Huang, Don Arnold, Joel D Hahn, Scott E Kanoski","doi":"10.1007/s00429-026-03164-y","DOIUrl":"10.1007/s00429-026-03164-y","url":null,"abstract":"<p><p>The ventral hippocampus contributes to food intake regulation and a range of motivational and memory processes, and its dysfunction is associated with several cognitive and behavioral disorders. However, its circuit-level organization remains incompletely understood. Ventral CA1 (CA1v) neurons send projections to several regions involved in motivational control. Here we focus on three major forebrain targets: the nucleus accumbens shell (ACBsh), medial prefrontal cortex (mPFC), and lateral hypothalamic area (LHA). We mapped the upstream and downstream circuitry of CA1v neurons defined by their projections to these target regions in rats using complementary transsynaptic anterograde and retrograde viral tracing approaches. Monosynaptic outputs to ACBsh, mPFC, and LHA were targeted using ATLAS, a novel transsynaptic anterograde viral approach that drives Cre recombinase in neurons receiving synaptic transmission from the CA1v. Second-order projections arising from these defined pathways were then mapped using a Cre-dependent anterograde viral tracing strategy. In parallel, upstream inputs to CA1v neurons projecting to each downstream target were mapped using a conditional retrograde glycoprotein-deleted rabies viral approach. Anterograde tracing revealed both shared and pathway-specific second-order targets, including bidirectional CA1v projections. Retrograde tracing confirmed expected inputs (e.g., CA3) and uncovered previously unrecognized cortical sources that differed across downstream projection-defined CA1v subpopulations. Together, these findings delineate pathway-specific, multi-node circuits linking CA1v neurons to key motivational systems that may inform future therapeutic strategies for disorders involving ventral hippocampal dysfunction.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simultaneous activation of border-associated immune cells and glial cells at the CNS-meningeal interface after subarachnoid haemorrhage in rats.","authors":"Thannoon Masood, Szandra Lakatos, Melissza Ignácz, Judit Rosta","doi":"10.1007/s00429-026-03156-y","DOIUrl":"10.1007/s00429-026-03156-y","url":null,"abstract":"<p><p>Border-associated macrophages (BAM) and mast cells are resident immune cells at the peripheral CNS borders, strategically located close to the brain surface, potentially influencing the homeostasis of the underlying parenchyma. Subarachnoid haemorrhage (SAH), when blood enters between the meningeal layers that cover the brain, is associated with neuroinflammation, which has been shown to play a critical role in subsequent brain damage; however, the impact of the activation of border-associated immune cells on the pathomechanism of the disease has not been investigated. Our aim was to examine inflammatory reactions that occur simultaneously at the cellular level in various compartments of the CNS: meningeal, subdural space, and parenchyma after experimental SAH in rats. Using immunohistochemistry, we performed the morphological characterisation of the BAM subpopulations in meningeal preparations. Additionally, confocal microscopy and image analysis were used to evaluate the reactive state of microglia cells and the integrity of the glial boundary in the upper fronto-parietal cortex of the rat 72 h after SAH. We demonstrated morphological alterations of BAM populations in the meninges and parallel disintegration of the astrocyte barrier due to haemorrhage. Furthermore, we confirmed the crucial role of mast cells in subsequent glial reactions. Our results suggest that activation of border-associated immune cells, contemporaneously with the early neuroinflammatory reactions that take place in the brain parenchyma, proposes a feasible signalling between these compartments following haemorrhage. Further studies are to be performed to reveal the importance of CNS meningeal border as a communication interface in the pathomechanism of SAH.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"231 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}