Search Results (4,847)

Background: Radiotherapy is essential for skull base tumor management but carries the risk of radiation-induced brain injury (RIBI). This spectrum ranges from transient radiation-induced contrast enhancement (RICE) to irreversible necrosis. Distinguishing these entities from tumor progression is critical, particularly with the increasing adoption of proton therapy. Methods: A comprehensive narrative review of the peer-reviewed literature was conducted up to October 1, 2025. The search strategy focused on adult patients treated for skull base malignancies, synthesizing data on dose–volume metrics, incidence rates, and modality-specific toxicity profiles. Results: RIBI represents a pathophysiological continuum. (a) Descriptive imaging patterns: In prospective proton therapy series, focal RICE occured in 15% of patients, typically at a median of 12 months, and often resolved spontaneously. (b) Modality comparison: Although proton therapy reduces integral brain dose versus photon therapy, elevated linear energy transfer (LET) at the distal Bragg peak may contribute to focal radiation-associated image changes (RAIC), particularly in the temporal lobes. (c) Risk stratification and diagnosis: Risk increased when >1% of the healthy brain received >57.6 Gy (Relative Biological Energy (RBE)) or when V67Gy exceeded 0.17 cc. Advanced MRI and amino acid positron emission tomography (PET) improved differentiation between radiation effects and tumor recurrence. Conclusions: Post-radiation imaging changes are common and often benign. Distinguishing RICE from progression requires multimodal imaging and adherence to specific dose constraints. Management should prioritize surveillance for asymptomatic lesions. Full article

Minimally invasive parafascicular surgery (MIPS) represents a paradigm shift in the management of deep-seated brain tumors, enabling function-sparing resections previously limited to biopsy and/or medical therapy. Central to MIPS are structured frameworks guiding preoperative planning and intraoperative execution. The six-pillar concept—comprising imaging, navigation, atraumatic access, optics, resection, and postoperative care—provides a comprehensive approach to integrate advanced neuroimaging, tractography, tubular retractor systems, fluorescence-guided resection, and neuromonitoring to optimize functional outcomes. Five-point target-trajectory complex planning—craniotomy, outer radial corridor, inner radial corridor, target, and resection margins—translates preoperative imaging and functional mapping into a precise surgical trajectory, balancing maximal tumor resection with minimal disruption of eloquent brain structures. Preoperative assessment of tumor characteristics, vascular relationships, and cortical eloquence informs trajectory planning and intraoperative adjustments. A critical determinant of MIPS success is the intraoperative golden hour, referring to the high-risk period surrounding brain cannulation with a tubular retractor. Key principles include (1) precannulation system checks to ensure instrument readiness; (2) access injury prevention through optimized craniotomy sizing and sulcal preparation; (3) tubular-tumor targeting accuracy addressing brain and tubular translation, tumor displacement, and white-matter sleeves; and (4) intracranial pressure control strategies to minimize tissue strain and venous congestion. Overcoming this period enables a controlled resection phase guided by the above-mentioned surgical adjuncts. The six-pillar concept and five-point target-trajectory complex planning are the foundations of MIPS planning, whereas the intraoperative golden hour provides a roadmap for successful intraoperative delivery of the surgical plan. Full article

Ischemic stroke induces complex molecular responses that disrupt subcellular organelles’ function and contribute to brain injury, yet the temporal changes of organelle-specific transcriptomic remodeling remain to be investigated. In this study, we performed in silico analysis of publicly available transcriptomic data from isolated brain microvessels of transient middle cerebral artery occlusion (tMCAO) mouse model. Using in silico approaches, we analyzed differential gene expression at 24 h (acute phase) and 7 d (intermediate phase) post-stroke, focusing on mitochondria, endoplasmic reticulum (ER), and Golgi apparatus. Functional enrichment (Gene Ontology, KEGG) and protein–protein interaction network analyses were performed. Our analysis of the data revealed that at 24 h post-stroke, all three organelles exhibited marked transcriptional remodeling, where mitochondrial pathways showed disrupted metabolic and redox regulation; ER pathways indicated activation of biosynthetic processes, stress signaling, and ferroptosis; and Golgi-related genes reflected altered vesicular trafficking and glycosylation. By 7 d, mitochondrial alterations subsided, whereas ER and Golgi pathways displayed downregulation of metabolic and neuronal signaling processes, indicating persistent dysfunction and incomplete microvascular recovery. Phase-specific drug–gene interaction analysis will be useful to understand temporal organelle-associated transcriptional organization and to guide future investigations of neurovascular remodeling after ischemic stroke. Full article

Inflammatory bowel disease (IBD) is increasingly recognized as a systemic inflammatory disorder associated with elevated long-term risk of ischemic stroke, even among younger individuals without traditional vascular risk factors. Although chronic inflammation, endothelial dysfunction, and hypercoagulability partially explain this association, the biological mechanisms linking intestinal inflammation to cerebral vascular injury remain incompletely defined. Extracellular vesicles (EVs), membrane-bound particles released by epithelial, immune cells and platelets, have emerged as potent mediators of intercellular communication in inflammatory states. In IBD, circulating EVs are enriched with pro-inflammatory cytokines, microRNAs, adhesion molecules, tissue factors, which are capable of promoting endothelial activation, blood–brain barrier disruption, immune-thrombosis and neuroinflammation. This review summarizes epidemiologic, vascular, and EV biology literature to propose a mechanistic framework in which EV-mediated signaling integrates intestinal inflammation with cerebrovascular vulnerability along the gut–vascular–brain axis. While direct causal evidence remains limited, converging mechanistic data supports biological plausibility and defines priorities for future experimental and translational investigation. Full article

Background/Objectives: Atrial fibrillation is the most common sustained arrhythmia and frequently occurs in the perioperative setting. However, its clinical relevance in neurosurgical patients remains poorly defined despite increased vulnerability related to brain injury, inflammation, and perioperative stress. This study aimed to determine whether newly detected postoperative atrial fibrillation (POAF) identifies a higher-risk profile and is associated with postoperative complications, resource utilization, and short-term mortality compared with patients remaining in sinus rhythm (SR). Methods: We conducted a single-center retrospective cohort study (October 2020–April 2025). Among 2619 neurosurgical procedures, only patients with both pre- and in-hospital post-procedure ECGs and no pre-existing arrhythmia were included. POAF was defined as atrial fibrillation detected on any post-procedure ECG. Outcomes were compared using Welch’s t-test, χ²/Fisher’s exact tests, and odds ratios (OR) with 95% confidence intervals (CI). This study was not designed to estimate the incidence of POAF but rather to compare outcomes within a selected ECG-screened subgroup. Results: A total of 171 patients met the inclusion criteria: 79 (46.2%) developed POAF and 92 (53.8%) remained in SR. Patients with POAF were older and had a higher burden of cardiometabolic comorbidities and were more likely to undergo craniotomy/trepanation and emergency procedures. Compared with SR, POAF was associated with higher rates of postoperative complications, longer ICU and hospital stay, lower likelihood of discharge home, and higher short-term mortality. These findings reflect a selected ECG-screened cohort and should not be interpreted as the incidence of POAF in the overall neurosurgical population. Conclusions: Newly detected POAF is associated with a higher-risk postoperative profile in neurosurgical patients. It clusters with greater comorbidity burden, more invasive and urgent procedures, increased complications, prolonged hospitalization, reduced likelihood of discharge home, and higher short-term mortality. These findings support further evaluation of rhythm surveillance and perioperative management strategies in higher-risk neurosurgical populations. Full article

Traumatic brain injury (TBI) represents a significant global health challenge with limited effective treatments. The secondary injury phase, characterized by persistent neuroinflammation, is a major contributor to long-term neurological deficits. Conventional therapies face substantial hurdles, including the blood–brain barrier (BBB), short therapeutic windows, and poor neuroregenerative capacity. Innovative biomaterials offer a promising platform to overcome these limitations by providing localized Drug Deliv., immunomodulation, and structural support for neural regeneration. This review outlines the pathological mechanisms of neuroinflammation and repair obstacles following TBI. It then systematically categorizes and discusses the mechanisms of various biomaterials—including natural, synthetic, nano-scale, composite, and intelligent materials—in modulating neuroinflammation. Furthermore, we elaborate on strategies for promoting neural repair, such as constructing regenerative scaffolds, delivering therapeutic agents (e.g., neurotrophic factors, stem cells, and exosomes), and remodeling the regenerative microenvironment. Special emphasis is placed on the emerging application of exosome delivery systems. Finally, we address the challenges in clinical translation and present future perspectives on smart materials, multi-modal systems, and personalized therapies, highlighting the transformative potential of biomaterials in TBI management. Full article

Background: Cardiopulmonary bypass (CPB) is an essential technique for cardiac surgery but significantly increases the risk of perioperative neurological complications. Electroencephalography (EEG) enables real-time monitoring of brain function and provides sensitive biomarkers for early detection of cerebral injury. However, a systematic synthesis of how CPB-related physiological, pharmacological, and technical factors influence EEG signals, and how these insights can be integrated into clinical decision-making, is still lacking. Objective: To systematically review the effects of temperature management, mean arterial pressure (MAP), hemodilution, anesthetic agents, embolization, and systemic inflammatory response during CPB on EEG parameters (including frequency bands, Bispectral Index (BIS), quantitative EEG metrics such as burst suppression ratio (BSR), spectral edge frequency (SEF), etc.), and to evaluate the associations between EEG changes and postoperative delirium (POD) and stroke. Methods: Following the PRISMA 2020 guidelines, we searched PubMed, Web of Science, and related databases for original English-language articles published between February 1974 and September 2025. Inclusion criteria: adult patients (≥18 years) undergoing cardiac surgery with CPB and intraoperative EEG monitoring (raw or processed). Exclusion criteria: reviews, case reports, animal studies, pediatric populations, and articles with inaccessible full texts. Two reviewers independently screened the literature and extracted data; a narrative synthesis was performed. Results: Fifty-one studies were included. Main findings: (1) Hypothermia: BIS decreases linearly with temperature (≈1.12 units/°C); electrocerebral silence occurs during deep hypothermic circulatory arrest; EEG recovery dynamics during rewarming predict POD. (2) MAP and cerebral perfusion: The rate of MAP decline (≥0.66 mmHg/s) is a stronger predictor of EEG abnormalities than the absolute MAP value; under fixed pump flow, some patients exhibit coexisting cerebral overperfusion and metabolic suppression. (3) Hemodilution: Maintaining hemoglobin ≥9.4 g/dL prevents EEG slowing; a drop below 9.2 g/dL significantly increases the risk of slowing. A ≥10% decrease in regional cerebral oxygen saturation (rSO₂) is associated with a 1.5-fold increased risk of burst suppression. (4) Anesthetic agents: Propofol maintains flow-metabolism coupling, and BSR reflects deep anesthesia better than BIS; sevoflurane and isoflurane impair autoregulation and suppress EEG. (5) Embolization and inflammation: EEG epileptiform discharges increase the risk of POD five-fold; a decrease in LIR predicts stroke (AUC 0.771) and POD (AUC 0.779); persistent EEG changes increase the risk of POD 2.65-fold. Conclusions: CPB-related factors affect EEG signals through distinct mechanisms, and specific EEG patterns (slowing, burst suppression, asymmetry, epileptiform discharges) are significantly associated with postoperative neurological complications. Multimodal monitoring (EEG + cerebral oximetry + hemodynamics) with clear intervention thresholds facilitates individualized brain protection. Future interventional studies using real-time EEG feedback are needed to confirm improvements in long-term neurological outcomes. Full article

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required > 24 h of invasive ventilation within the first 3 days of life. Perinatal–neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary–venous) and the maximum and minimum PCO₂ in the first 72 h were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia as < 35 mmHg, and hypercapnia as > 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD. Full article

Traumatic brain injury (TBI) is a major cause of death and disability, mainly in persons under 45 years of age and it remains clinically challenging due to its heterogeneous pathophysiology and unpredictable course. Except from the initial mechanical damage, secondary injury —largely driven by neuroinflammation—plays a critical role in outcome and extent of recovery. Cytokines are central mediators of this immune response and have therefore been extensively studied as potential biomarkers for TBI diagnosis, need of imaging and prognosis. Among pro-inflammatory cytokines, IL-1β is rapidly upregulated after TBI and contributes to blood–brain barrier disruption and secondary damage. Furthermore, experimental studies suggest that IL-1 inhibition could be neuroprotective. IL-6 is up to date the most extensively studied cytokine and shows strong associations with injury severity, neuroimaging abnormalities, mortality and long-term functional outcomes across multiple adult and pediatric studies. Nevertheless, results vary depending on the biological compartment and timing. Anti-inflammatory IL-10 levels correlate with injury severity and has shown promise in distinguishing CT-positive from CT-negative mild TBI patients, potentially reducing unnecessary imaging, though findings are inconsistent. Other cytokines, including IL-17, TNF-α, IL-8, IL-9, and IL-15, have been correlated to post-traumatic neuroinflammation and may have diagnostic or prognostic value. Overall, IL-6 and IL-10 currently appear to be the most promising cytokine as biomarkers, however future research should focus on standardized cytokines assessment methods and possible use of multimarker panels. Full article

Mild traumatic brain injury (mTBI) contributes substantially to years lived with disability (YLD), decreases health-related quality of life, and imposes significant costs on healthcare systems and society. Millions of people experience mTBI each year, and healthcare costs for mTBI in just the first year after injury exceed $44 billion USD. Despite the common occurrence of mTBI, estimates of incidence, prevalence, related disability, and costs vary widely. This variance is attributed to the underreporting of head impacts, inconsistent definitions of mTBI, and a lack of objective biomarkers. Currently available clinical blood biomarkers primarily assist in ruling out CT-detectable intracranial injury rather than definitively diagnosing mTBI itself, underscoring the continued need for objective, portable, and clinically specific biomarkers. Numerous imaging findings, blood proteins, and physiological measures are under investigation for these purposes, and some may have multiple uses. Specific biomarkers for acute diagnosis are needed urgently. Although many systematic reviews have been published, most focus on a single biomarker or class of biomarkers. Given the breadth of potential biomarker categories, conducting a comprehensive, systematic review across modalities is challenging. Here, we provide a narrative review summarizing the extant literature across major biomarker domains studied in adolescents and adults. We emphasize candidates supported by the most robust evidence to guide continued research and clinical translation. Full article

2S/LGBTQIA+ survivors of intimate partner violence (IPV) face multiple, intersecting barriers to accessing care, yet little is known about how these barriers are shaped by IPV-caused brain injury (IPV-BI). Background/Objectives: This study aimed to explore how stigma and institutional trust influence 2S/LGBTQIA+ survivors’ experiences of help-seeking following IPV-BI. Guided by a Community Advisory Board, four semi-structured focus groups were conducted with 29 2S/LGBTQIA+ IPV-BI survivors. Methods: Reflexive thematic analysis was used to examine participants’ help-seeking accounts, with attention to minority stress and intersecting stigmas related to IPV, BI, and 2S/LGBTQIA+ identity. Results: The findings indicate that survivors navigated compounded stigmas that limited access to safe, affirming services and heightened vulnerability during help-seeking. Institutional trust was central to participants’ decisions to disclose sensitive information and engage in care, with confidentiality emerging as a critical determinant of perceived safety. Participants described negotiating disclosure, anticipating discrimination, and avoiding services when systems were perceived as unsafe or unresponsive. Conclusions: These findings highlight the need for service systems to integrate IPV-BI into screening and support protocols, provide training on the intersections of IPV, BI, and 2S/LGBTQIA+ identities, and centre confidentiality as a condition for trust and access, ultimately fostering safer, more responsive systems of care. Full article

Intracerebral hemorrhage induces severe secondary brain injury characterized by excessive neuroinflammation and inefficient hematoma clearance, processes largely governed by microglial polarization and phagocytic activity. The immunoproteasome, an inducible proteasome isoform involved in immune regulation, has been implicated in inflammatory neurological disorders, but its role in microglial responses after ICH remains unclear. In this study, rat models of common hemorrhage, severe hemorrhage, and severe hemorrhage with hematoma aspiration were used to represent graded injury severity and post-evacuation recovery. Transcriptomic profiling at day 3 post-injury identified immunoproteasome-associated gene networks, while expression of the catalytic subunits LMP2 and LMP7, microglial polarization markers, and phagocytic receptors was analyzed by Western blotting and immunofluorescence. Severe hemorrhage markedly induced LMP2 and LMP7 expression, predominantly in Iba1⁺ microglia, accompanied by enhanced ER stress, NF-κB signaling, and M1-like polarization and reduced phagocytic marker expression. Hematoma aspiration attenuated immunoproteasome expression and restored M2-associated and phagocytic signatures. Consistently, pharmacological inhibition of immunoproteasomes in primary microglia enhanced erythrophagocytosis and promoted a reparative phenotype in vitro. These findings indicate that immunoproteasome activation links hemorrhagic severity to maladaptive microglial polarization and impaired hematoma clearance after ICH, and that reducing immunoproteasome expression may help rebalance inflammatory and phagocytic microglial functions. Full article

Astrocytes undergo pronounced reactivity during traumatic brain injury (TBI); however, the temporal dynamics of this response and the signaling mechanisms regulating astrocyte proliferation remain incompletely defined. In this study, we characterized the spatiotemporal profile of astrocyte reactivity and proliferation in the hippocampus during TBI and investigated the involvement of mammalian target of rapamycin complex 1 (mTORC1) signaling in these processes. Using a mouse model of TBI, we found that injury triggered a rapid astrocytic response in the hippocampus, characterized by increased glial fibrillary acidic protein (GFAP) expression and morphological hypertrophy as early as 4 h post-injury. Astrocyte proliferation emerged subsequently, peaked during the acute phase (48 and 72 h), and declined to baseline levels at 7 days post-trauma, indicating a transient proliferative response during TBI. Concurrently, mTORC1 signaling was robustly activated in reactive astrocytes in the hippocampus and was specifically associated with proliferative reactive astrocytes during injury. Pharmacological inhibition of mTORC1 signaling with rapamycin significantly reduced reactive astrocyte proliferation during TBI without altering astrocytic hypertrophy. Together, these findings demonstrate that TBI induces a rapid but transient astrocyte activation and proliferation response in the hippocampus and that mTORC1 activation is required for the proliferation, but not the hypertrophic activation, of reactive astrocytes during traumatic brain injury. Full article

Regenerative medicine is becoming more widely integrated with longevity-oriented and preventive care as populations age and chronic degenerative diseases burden healthcare systems. Mesenchymal stem cell (MSC) therapies have progressed from experimental interventions to approved products, yet scalability, safety, cost, and regulatory complexity constrain widespread implementation in medical wellness contexts. The predominant therapeutic effects of MSCs are mediated via paracrine mechanisms, leading to cell-free approaches based on the MSC secretome—a complex mixture of bioactive factors including all types of biomolecules and assemblies thereof, such as exosomes. These acellular products offer compelling advantages: multiple batches from single-donor sources, standardized dosing, reduced allogeneic cell risks, and shorter outpatient-compatible administration. Preclinical and clinical data indicate that secretome-based products exert potent regenerative effects in osteoarthritis, chronic wounds, stroke, traumatic brain injury, and neurodegenerative diseases. This review examines the evolution from cell-based to cell-free regenerative strategies, focusing on human umbilical cord Wharton’s jelly MSC secretome for precision longevity medicine. It compares MSC therapies with secretome- and exosome-based formulations across mechanistic, manufacturing, safety, practical and regulatory dimensions. Regional perspectives highlight Southeast Asia, and especially Thailand, as an emerging regenerative-longevity hub. Finally, it outlines the preventive patient journey integrating cell-free interventions within multi-modal programs aimed at extending healthspan. Full article

Neurodegenerative diseases involve progressive neuronal loss associated with oxidative stress (OS) and inflammation. Given the limited efficacy of current therapies, natural compounds with multitarget neuroprotective potential are of growing interest. In this study, we investigated the neuroprotective effects of a standardized Magnolia officinalis (L.) bark extract (MOE) in rat brain cortical slices exposed to hydrogen peroxide-induced OS. MOE significantly recovered tissue viability and reduced ROS and malondialdehyde levels caused by OS while attenuating caspase-3, -8, and -9 activation, suggesting modulation of intrinsic and extrinsic apoptotic pathways. Shotgun proteomics using LC-HRMS/MS identified OS-induced protein expression changes reversed by MOE, with fourteen of thirty-three altered proteins rescued by MOE co-treatment. These proteins participate in several processes, including neuronal survival, OS response, and proteostasis. Bioinformatic analysis demonstrated that genes responsible for protein synthesis regulated by MOE are subjected to transcriptional regulation by factors associated with OS, including FOXO4, NRF2, and SP1. The present findings support the hypothesis that MOE exerts multitarget neuroprotective effects by modulating key proteins involved in OS responses and neuronal survival in an acute ex vivo oxidative injury model, suggesting potential relevance for mechanisms associated with NDs. Full article