The aberrant right subclavian artery (ARSA) is the most common anomaly of the arch of aorta and is significantly associated with a non-recurrent laryngeal nerve (NRLN). Nevertheless, the co-occurrence of ARSA with complex thoracic wall vascular remodeling is scarcely described in the current literature. This exploration describes an unusual group of neurovascular variations with important surgical significance. A precise dissection was performed on a 43-year-old female donor of Thai descent embalmed with soft-embalming technique with vascular silicone-color injection. The cervical and upper thoracic regions were dissected with emphasis on neurovascular pattern, and morphometric measurements. A retroesophageal ARSA was found to be the fourth branch of the aortic arch after the left subclavian artery, without a Kommerell diverticulum. A right-sided NRLN was confirmed to arise directly from the vagus nerve to then travel upwards next to the larynx. Crucially, the right internal thoracic artery (ITA) was completely absent, and its usual vascular territory was replaced by the superior intercostal artery (SIA) arising from the inferior aspect of the ARSA. Moreover, a separate muscular branch of the proximal ARSA was observed to provide blood supply to the left longus colli muscle. The current report describes a novel association of ARSA, NRLN, complete absence of the right ITA with a compensatory SIA and a muscular branch from the ARSA to the left longus colli muscle. This research emphasizes the embryological connection of the development of the cervical and thoracic vessels and indicates that thorough preoperative imaging is required to prevent any iatrogenic injury during surgery of the thyroid gland, cervical spine, esophagus and coronary bypass surgeries.
Spaceflight-Associated Neuro-ocular Syndrome (SANS) has emerged as a critical neuro-ophthalmic risk for human space exploration, particularly as mission duration increases and access to space expands. Current spaceflight ocular surveillance and research protocols have prioritized structural imaging and selected neuroimaging/physiological assessments. However, accumulating evidence suggests that SANS is not confined to the posterior pole as a purely structural optic nerve head phenomenon but may also involve vascular and hemodynamic alterations. At the same time, structural changes at the optic nerve head may not fully capture the functional integrity of the afferent visual pathway. We therefore propose to define a more targeted extension of current SANS surveillance protocols incorporating ultra-widefield swept-source optical coherence tomography angiography (UWF-SS-OCTA), visual evoked potentials (VEPs) and pattern electroretinogram (ERG) into standardized pre-flight, in-flight (when feasible), and post-flight assessments. Beyond its relevance to astronaut health, this topic may also be of translational interest to the broader scientific and clinical community.
Parkinson's disease (PD) is a progressive neurodegenerative illness characterized by loss of dopaminergic neurons and misfolded α-synuclein aggregation. The pathophysiology of PD involves the interplay of oxidative stress, neuroinflammation, and genetic variables. This review provides an overview of the ways oxidative stress and neuroinflammation interact with genetic and epigenetic pathways in PD, as well as how omics technologies have aided in the identification of biomarkers that can be targeted by treatments. This study was conducted as a narrative review. Using terms such as "Parkinson's disease," "oxidative stress," "neuroinflammation," "biomarkers," "genetics," and "omics," a literature search was conducted in PubMed, Web of Science, and Scopus for research published between January 2012 and December 2025. Studies pertinent to PD-related molecular processes and biomarkers were included after articles were filtered based on titles and abstracts; non- English publications were eliminated. According to recent research, oxidative stress and inflammation create a positive feedback loop that promotes neuronal death. The genes SNCA, LRRK2, and PINK1 have been associated with impaired mitochondria and mitophagy. PD-related RNA alterations, DNA methylation changes, and dysregulated miRNAs were discovered using omics approaches such as transcriptomics, epigenomics, and epitranscriptomics. BDNF, 8-OHdG, DJ-1, and phosphorylated α- synuclein are potential biomarkers for disease monitoring and diagnosis. In PD, oxidative stress and neuroinflammation work in combination with genetic, epigenetic, and epitranscriptomic dysregulation to cause dopaminergic neurodegeneration. This highlights the importance of multi-omics integration for identifying reliable biomarkers and disease- modifying therapeutic targets. Precision medicine is facilitated by an integrative, multi-omics-driven strategy that improves our understanding of the molecular pathophysiology of PD. Future research should focus on validating biomarkers, conducting longitudinal studies, and translating molecular discoveries into personalized treatments.
Diabetic silent myocardial ischemia (DSMI) represents a clinically underappreciated yet life-threatening cardiovascular complication in which impaired myocardial perfusion occurs without recognisable symptoms. Two converging pathological axes underlie this phenotype: coronary microvascular dysfunction and neurocardiac signalling disruption. Chronic hyperglycaemia drives oxidative stress, advanced glycation end-product (AGE) accumulation, and mitochondrial dysfunction in endothelial and smooth-muscle cells, collectively impairing nitric oxide (NO) bioavailability, coronary flow reserve, and capillary integrity. Simultaneously, diabetic peripheral and autonomic neuropathy attenuates nociceptive transmission and disrupts neurovascular coupling, blunting the perception of ischaemic pain. At the molecular level, dysregulated insulin receptor (INSR), angiotensin II type 1 receptor (AT1R), toll-like receptor 4 (TLR4), AMP-activated protein kinase (AMPK), and transient receptor potential (TRP) channel signalling converge to perpetuate endothelial injury, vascular inflammation, and neural dysfunction. Critically, emerging evidence implicates mitochondrial reactive oxygen species (mtROS) overproduction, impaired mitochondrial biogenesis, and altered mitochondrial dynamics as shared mechanistic nodes linking both axes. This review synthesises current mechanistic knowledge within a novel unified framework, proposes candidate biomarkers including urinary 8-OHdG, NT-proBNP, heart rate variability indices, and coronary flow reserve by cardiac PET/CMR and identifies actionable therapeutic targets, including mitochondria-directed antioxidants (MitoQ, SS-31), SGLT2 inhibitors, GLP-1 receptor agonists, TLR4 antagonists, and TRPV1 modulators. Testable mechanistic hypotheses and directions for future translational research are proposed to accelerate early diagnosis and disease-modifying intervention in high-risk diabetic patients.
Diabetic foot ulcer (DFU) is a common and clinically challenging chronic complication of diabetes, characterized by impaired healing, recurrent infections, and high amputation risk. Traditional treatments show limited efficacy in promoting neurovascular regeneration and tissue repair. In the field of tissue engineering, both electrospun nanofiber scaffolds and mesenchymal stem cells (MSCs) therapy have demonstrated considerable potential. Electrospun nanofibers closely imitate the structure and function of the native extracellular matrix (ECM). Furthermore, they can be functionally modified through directed strategies to incorporate antibacterial agents and various anti-inflammatory and pro-healing cytokines, thereby addressing multiple aspects of the DFU microenvironment. In contrast, MSCs play a crucial role in promoting wound healing owing to their paracrine signaling, immunomodulatory capabilities, and multidirectional differentiation potential. This review comprehensively summarizes the pathogenesis of DFU, the respective advantages of electrospun nanofibers and MSCs, and the latest research progress on their combined application for DFU treatment.
Alzheimer disease (AD) affects millions globally, but current diagnostic approaches typically can be costly and invasive. Accessible, noninvasive screening tools for early detection of cognitive impairment are needed. To determine whether optical coherence tomography angiography (OCTA)-based biomarkers of the retina, choroid, and choriocapillaris differ across cognitive states and whether these biomarkers might discriminate among normal cognition, mild cognitive impairment (MCI), and AD dementia. This cross-sectional study enrolled 103 individuals referred from the University of Washington Alzheimer's Disease Research Center (ADRC) between April 2022 and September 2024. Participants included 49 cognitively normal controls, 29 with MCI, and 25 with AD dementia per ADRC research-criteria evaluations. All participants underwent swept-source OCTA (SS-OCTA). These data were analyzed from February 2025 to March 2026. Cognitive status, retinal vessel skeleton density (VSD), choriocapillaris flow deficit (CCFD), and ganglion cell complex (GCC) thickness. Among 103 participants (mean [SD] age, 74.8 [6.72] years; 50 [48.5%] female and 53 male [51.5%]), the adjusted mean GCC was thinner in AD dementia (63.31 μm) vs controls (67.93 μm) (difference, -4.62 μm; 95% CI, -8.92 to -0.31 μm; P = .03). Adjusted mean CCFD was lower in MCI (8.12%) than AD dementia (9.07%) (difference, -0.95%; 95% CI, -1.71 to -0.19; P = .01) but higher in AD dementia than controls (8.33%) (difference, 0.74%; 95% CI, 0.02-1.46; P = .04). In multivariable models, VSD (MCI: odds ratio [OR], 0.79; 95% CI, 0.77-0.81; AD dementia: OR, 0.66; 95% CI, 0.65-0.68; P < .001) and CCFD (MCI: OR, 0.66; 95% CI, 0.65-0.67; AD dementia: OR, 1.50; 95% CI, 1.49-1.52; P < .001) were significantly associated with cognitive status, with an area under the curve of 0.72 to 0.87 in a 21-participant test set (10 controls, 6 MCI, 5 AD dementia). In a relatively small cohort study, OCTA revealed distinct microvascular signatures across cognitive stages. VSD decreased, and CCFD showed a biphasic pattern across cognitive stages in multivariable models, which may suggest early compensatory choriocapillaris hyperperfusion followed by perfusion failure in AD dementia. These findings suggest OCTA biomarkers may serve as accessible, noninvasive indicators of cognitive neurodegeneration, warranting larger longitudinal validation.
Reconstruction of large segmental bone defects remains challenging because current grafting strategies often fail to coordinate angiogenesis, neurogenesis, and osteogenesis. Here we developed a functional scaffold (peptide/Talin1 plasmid/PLA-HA/GelMA, PTPG) capable of simultaneously delivering peptides and Talin1 plasmids. We hypothesized that this scaffold enables neurovascularized bone regeneration through bidirectional activation of integrin β1 (ITGB1). The REDV-IKVAV (Arg-Glu-Asp-Val-Gly-Gly-Gly-Ile-Lys-Val-Ala-Val) peptide triggers "outside-in" ITGB1 signaling in endothelial and Schwann cells, while Talin1 plasmid-mediated "inside-out" activation. This PTPG scaffold synergistically enhances cell proliferation, migration and secretion, which are eliminated by ITGB1 silencing. In vivo, PTPG scaffold promotes aligned neurovascular networks guiding bone deposition. Single-cell RNA sequencing demonstrates enrichment of endothelial H-type signatures and repair-associated Schwann cell phenotypes, with activation of ITGB1-focal adhesion kinase-paxillin signaling. Collectively, this scaffold integrates structural support with peptide and genetic cues to promote coordinated angiogenesis, neurogenesis, and osteogenesis, offering a promising strategy for functional bone regeneration.
Rosacea and migraine are prevalent chronic disorders traditionally viewed as distinct conditions affecting separate organ systems. However, emerging evidence suggests a significant overlap, notably through shared neurovascular and neuroinflammatory pathways. This literature review explores the mechanisms linking rosacea, a chronic inflammatory skin condition characterized by facial flushing and sensitivity, and migraine, a neurological disorder marked by recurrent headaches. Current research highlights the critical roles of neuropeptides, including calcitonin gene-related peptide (CGRP), substance P (SP), and pituitary adenylate cyclase-activating polypeptide (PACAP), in mediating inflammation and vascular dysregulation common to both conditions. Despite these advances, notable gaps remain, such as limited data on the impact of migraine treatments (e.g., CGRP inhibitors) on rosacea, unclear reasons behind the selective comorbidity of these conditions, minimal research comparing rosacea to other headache disorders, and methodological limitations across studies. Addressing these gaps through interdisciplinary research holds promise for improved clinical outcomes. This review underscores the importance of recognizing rosacea and migraine as interrelated neurovascular disorders, advocating for integrated therapeutic approaches, and proposing directions for future research.
To describe the most commonly used interventions for the management of trigeminal neuralgia (TN), a neurological disorder characterized by episodes of intense, paroxysmal facial pain that severely affect quality of life and interfere with daily activities such as eating, speaking, and maintaining oral hygiene. Scoping review. A systematic search was conducted in PubMed, Scopus, EMBASE, Web of Science, and PsycINFO databases. Articles published between 2020 and 2025, written in English or Spanish, involving adults aged over 18 years and addressing interventions for TN, including pharmacological, surgical, and noninvasive treatments, were considered eligible. Studies were screened by title, abstract, and full-text review according to predefined eligibility criteria. The review focused on identifying and mapping the range of interventions used in TN management. Thirty-seven articles met the inclusion criteria and were included in the final synthesis. Most of the included studies investigated minimally invasive interventions, particularly percutaneous rhizotomy, followed by noninvasive approaches such as neuromodulation techniques and invasive procedures including microvascular decompression. The evidence suggests that TN management requires a multimodal approach, with pharmacological therapy as the first-line treatment and surgical or neuromodulation procedures reserved for refractory cases. Treatment selection should consider pain severity, response to medication, and the presence of neurovascular compression. Complementary therapies may also contribute to improving patient outcomes, although further research is needed to establish their effectiveness. An individualized treatment approach is essential to optimize pain control and improve quality of life in individuals with TN. Integrating pharmacological, surgical, and noninvasive strategies according to patient characteristics and clinical presentation may enhance treatment effectiveness and functional outcomes.Nursing Practice. These findings emphasize the importance of systematic pain assessment, patient education regarding pharmacological management, monitoring for adverse effects associated with interventional procedures, and the implementation of psychosocial support strategies. Nurses play a key role in promoting treatment adherence, identifying unmet supportive care needs, and improving the overall quality of life of individuals living with TN.
Encephalopathy is a common complication of sepsis, occurring in up to 70% of patients admitted to the intensive care unit. It is primarily characterized by a deterioration in condition, ranging from delirium to coma, but also by electroencephalographic changes and seizures. Sepsis-associated encephalopathy (SAE) is linked to increased mortality, which rises in proportion to the severity of both clinical manifestations and electroencephalographic abnormalities, and is frequently followed by long-term cognitive impairment and functional disability. The pathophysiology of SAE is complex and includes a disturbance in neurotransmission together with a dysfunction of different brain cells and functional complexes (blood-brain barrier, neurovascular coupling, synapses). Neuroinflammation and ischemia are its main processes. Its cellular mechanisms include bioenergetic failure and oxidative stress. The frontal cortex, hippocampus, limbic system, and brainstem are particularly vulnerable to these events. Currently, management relies primarily on controlling sepsis and applying recommendations for delirium, including the avoidance of neurotoxic agents. Developing a specific treatment would depend on a better understanding of its pathophysiology, through a relevant experimental model, as well as on the identification of biomarkers with diagnostic, pathophysiological, and/or prognostic value. This contemporary review synthesizes current data on the epidemiology, mechanisms, characteristics and complications of SAE, as well as priorities for therapeutic progress.
The meniscus is critical for load distribution and joint stability; tears disrupt biomechanics and accelerate cartilage degeneration, prompting a shift from meniscectomy toward preservation and repair. We review three core techniques - inside-out, outside-in, and all-inside - with stepwise descriptions, indications, advantages/limitations, devices, and complication profiles. Inside-out offers precise, strong fixation but requires an accessory incision and neurovascular precautions; outside-in is reproducible and cost-efficient for anterior horn tears; and all-inside reduces soft-tissue dissection and operative time, improving access to posterior/body regions. No single meniscal repair technique demonstrates clear superiority in healing or failure rates; outcomes depend on tear characteristics and patient factors. Although modern all-suture all-inside devices show favorable biomechanics, their higher cost and unclear cost-effectiveness limit definitive clinical advantage. Technical pearls include optimized portal placement, peripheral bites, protection of neurovascular structures, and avoidance of soft-tissue bridges. Concomitant ACL reconstruction enhances healing - likely via improved stability and marrow-derived biologic augmentation. Region-specific guidance is provided using medial and lateral anatomical zoning, aligning suture patterns (inside-out, outside-in, and all-inside) to tear location to preserve biomechanics and reduce complications.
The retina and optic nerve rely on a tightly regulated neurovascular unit that sustains the highly dynamic and metabolically demanding neural tissues required for vision. Adequate oxygen and nutrient delivery are essential for maintaining tissue function and cellular survival. Over the past decades, extensive research within and beyond the field of ophthalmology has sought to elucidate the mechanisms that govern neurovascular regulation in health and disease. Growing evidence indicates that neurovascular dysfunction plays an important role in both the initiation and progression of glaucoma, a leading cause of irreversible blindness worldwide. Alterations in vascular architecture and blood flow may compromise the metabolic support required by retinal ganglion cells, increasing their vulnerability to injury and degeneration. While neurons possess limited regenerative capacity, the vascular system retains a remarkable degree of plasticity and is therefore amenable to repair. This vascular plasticity presents an opportunity to develop therapeutic strategies aimed at restoring vascular architecture and improving blood flow, complementing existing approaches focused on intraocular pressure reduction, neuroprotection, axonal regeneration, and/or neuronal transplantation. In this review, we summarize the current understanding of neurovascular function in the healthy eye, discuss mechanisms that contribute to vascular compromise in glaucoma, and highlight emerging avenues for promoting vascular regeneration and blood flow recovery. By identifying key knowledge gaps and future research priorities, we aim to outline promising directions for targeting the ocular neurovasculature to preserve retinal ganglion cell function and slow or stop progressive vision loss.
The recent focus on improving quality and reducing cost within the US healthcare system has increased care being performed in the outpatient setting. The impact on neurosurgeons' practice patterns has not yet been fully elucidated. In addition, how this transition may affect neurosurgery resident training is unclear. To better understand these issues, we surveyed neurosurgeons. A 13-question survey was sent to Council of State Neurosurgical Societies email subscribers. The survey focused on training or practice level, location, practice setting, ambulatory surgical center (ASC) utilization, and types of procedures performed at ASCs. Responses were tabulated. Statistical analysis was performed. Among 11,091 subscribers, 101 responses (0.9%) were recorded. Most of the respondents (57.4%) utilized an ASC in their practice. The commonly performed procedures were microdiscectomy (98.1%), hemilaminectomy (94.2%), battery changes (87.5%), single-level anterior cervical discectomy and fusion (84.6%), single-level lumbar or thoracic laminectomy (80.8%), and peripheral nerve decompression (66.7%). Cranial procedures were seldom performed. Other device-related procedures were common and included vagal nerve stimulation (32.5%), spinal cord stimulation (67.5%), baclofen pump placement (25%), and baclofen pump replacement (27.5%). Only 17.1% of respondents who worked in academia taught residents in an ASC. According to our survey results, most neurosurgeons have incorporated ASCs into their practices in some capacity and most frequently for simple spine procedures, device-related procedures, and peripheral nerve decompression. The limited resident involvement in procedures in the ASC setting, even among attending academic neurosurgeons, suggests an increased need for ASC incorporation in residency training.
Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and is increasingly recognized as a complex neurovascular disease characterized by early neuroinflammation, neurodegeneration, and microvascular dysfunction. Current therapies primarily target late-stage vascular complications and do not adequately address the upstream mechanisms involved in DR onset and progression. Minocycline, a second-generation semisynthetic tetracycline with high lipophilicity, has emerged as a promising therapeutic candidate because of its pleiotropic pharmacological effects beyond antimicrobial activity. Accumulating experimental evidence indicates that minocycline exerts anti-inflammatory, anti-apoptotic, mitochondrial-protective, and potentially epigenetic regulatory effects in diabetic retinal tissues and cellular models. Mechanistically, minocycline suppresses microglial activation, attenuates pro-inflammatory signaling, stabilizes the blood-retinal barrier, preserves mitochondrial function, inhibits matrix metalloproteinase activity, and has been associated with changes in histone acetylation and methylation under diabetic conditions. These actions may help preserve retinal neurovascular integrity and reduce neuronal and microvascular injury in experimental DR models. Despite promising preclinical findings, clinical evidence remains limited. Early-phase clinical studies indicate that oral minocycline is generally well tolerated; however, its efficacy has not been established in adequately powered clinical trials. This review summarizes the pharmacological properties of minocycline, critically examines its molecular mechanisms in DR pathogenesis, and discusses current clinical evidence, translational challenges, and future research directions. Although available data support further investigation of minocycline for DR, additional preclinical and clinical studies are needed to determine its therapeutic efficacy and clinical applicability.
The relationship between structural and functional damage in glaucoma, the structure-function relationship, forms the cornerstone of disease assessment, monitoring, and prognosis. We provide an updated synthesis of current knowledge on the structure-function relationship, emphasizing recent advances in imaging, analytical methodologies, and artificial intelligence (AI)-driven modelling. We summarize merging evidence from optical coherence tomography (OCT), OCT angiography, and related imaging technologies, highlighting their integration with functional measures such as standard automated perimetry. We also evaluate classical, mechanistic, statistical, and hybrid models that link retinal microstructure and visual function and discusses the role of AI-based approaches in predicting visual field loss and improving clinical interpretation. The structure-function relationship in glaucoma is predominantly nonlinear for currently used clinical metrics, reflecting biological redundancy, psychophysical variability, and measurement constraints with current tools. Stage-dependent changes reveal strong correlations during moderate disease but increasing divergence in early and advanced stages due to floor effects and functional compensation. Emerging frameworks, such as anatomically compensated mapping, multimodal fusion, and deep learning, enhance accuracy and allow individualized structure-function relationship modelling. Data quality, myopia-related anatomical variability, and cross-device harmonization remain key limitations. Integrating multimodal imaging, AI-based harmonization, and longitudinal data will advance structure-function relationship modelling beyond static correlations toward dynamic, personalized biomarkers of neurovascular and neurofunctional health. These developments promise earlier detection, more precise monitoring, and individualized glaucoma management through a deeper mechanistic understanding of the link between retinal structure and visual function.
Vascular dementia (VaD) is the second most prevalent form of dementia, accounting for 15%-20% of dementia cases and is primarily caused by cerebrovascular disorders. Current treatments predominantly focus on risk factor management and symptom alleviation, lacking the ability to cure the disease or reverse cognitive decline, which underscores the urgent need for novel therapeutic approaches like nanotechnology. This paper provides a comprehensive review integrating materials science, clinical medicine, and bioinformatics to evaluate the current status of nanomaterial research in VaD. It focuses on the molecular mechanisms of action of various nanomaterials and provides an analysis of their therapeutic potential and future development challenges. In diagnostic applications, nanomaterials (e.g., SPIONs and fluorescent nanoparticles) enable high-contrast imaging of early-stage vascular inflammation, blood-brain barrier (BBB) leakage, and amyloid β (Aβ) deposits. In therapeutic applications, engineered nanocarriers (including liposomes, polymeric nanoparticles, and gold nanoparticles) exhibit specific targeting, controlled release, and BBB penetration capabilities. They mitigate VaD pathology by promoting angiogenesis, scavenging reactive oxygen species (ROS) to reduce oxidative stress, inhibiting neuroinflammation, protecting the neurovascular unit (NVU), and facilitating white matter repair. Nanotechnology provides an innovative framework for the diagnosis and treatment of VaD through intelligent, targeted drug delivery systems. Future advancements require establishing systematic biocompatibility evaluation frameworks, addressing long-term toxicity concerns, and expanding multicenter clinical trials to validate safety and efficacy for clinical translation.
Neurological disorders, including Alzheimer's disease, Parkinson's disease, and stroke, remain major causes of global disability and mortality, with limited neuroprotective therapies available. Traditional Chinese medicine (TCM) offers multi-target therapeutic potential, but its mechanistic complexity requires systematic investigation using appropriate model systems. Zebrafish (Danio rerio) has emerged as a valuable vertebrate platform for TCM neuroprotection research due to its genetic homology with humans, optical transparency, and high-throughput screening compatibility. This review summarizes the application of zebrafish models in studying TCM for Alzheimer's disease, Parkinson's disease, cerebral ischemia, epilepsy, insomnia, depression, and spinal cord injury. Key findings indicate that TCM metabolites exert neuroprotective effects through multiple mechanisms, including anti-oxidative stress, anti-neuroinflammation, anti-apoptosis, neurotransmitter modulation, neurogenesis promotion, and vascular protection. Zebrafish models have proven particularly useful for high-throughput screening of active metabolites, real-time in vivo imaging of neurovascular processes, and rapid safety assessment. However, limitations such as the absence of a layered neocortex, differences in drug metabolism, and the predominantly acute nature of current models must be acknowledged. Addressing these challenges through model standardization, multi-omics integration, and cross-species validation will further enhance the translational relevance of zebrafish-based TCM research. This review provides a practical framework for leveraging zebrafish models to advance the mechanistic understanding and clinical development of neuroprotective TCM therapies.
Proliferative diabetic retinopathy (PDR) is a leading cause of severe vision loss in working-aged adults and represents the end stage of chronic neurovascular injury in diabetes. Despite advances in screening and treatment, including panretinal photocoagulation (PRP), intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, and pars plana vitrectomy (PPV), outcomes remain heterogeneous: many eyes stabilise, whereas others progress to vitreous hemorrhage, tractional retinal detachment, or neovascular glaucoma despite apparently adequate therapy. This review synthesizes current knowledge on the pathophysiology, morphological phenotypes and treatment paradigms of PDR, with a specific focus on predictors of onset, progression, and recurrence. PDR is contextualised as a multifactorial neurovascular and inflammatory disease, integrating data on hypoxia-driven angiogenesis, glial activation, microvascular rarefaction, neurodegeneration, and vitreoretinal interface remodeling. Histopathological and multimodal imaging characteristics of neovascular complexes and the vitreoretinal interface are described, highlighting how phenotypes on color fundus photography, widefield fluorescein angiography, optical coherence tomography (OCT), and OCT angiography relate to ischemic burden and clinical behaviour. Systemic, ocular, imaging, biomarker, and genetic factors associated with progression from non-proliferative diabetic retinopathy to PDR and with progression within established PDR after PRP, anti-VEGF therapy, and PPV are critically appraised. Across modalities, younger age, diabetes duration, poor glycemic control, renal disease, extensive non-perfusion, high neovascular burden, complex fibrovascular proliferation, and incomplete or unsustained treatment consistently emerge as determinants of guarded outcomes. Outstanding gaps in mechanistic understanding, risk stratification, regenerative therapy, and implementation are identified, alongside a proposed research agenda aimed at delivering mechanistically grounded risk-prediction tools and disease-modifying interventions for PDR.
Perioperative neurocognitive disorders (PND), including postoperative delirium, delayed neurocognitive recovery, and postoperative neurocognitive disorder, are important complications in older and vulnerable surgical patients. These conditions are associated with prolonged hospitalization, reduced functional recovery, greater healthcare utilization, and worse longer-term outcomes. Current evidence indicates that PND is not driven by a single mechanism. Instead, systemic inflammation, neurovascular dysfunction, blood-brain barrier injury, glial activation, innate immune signalling, and synaptic injury are all thought to contribute. However, the pathways by which peripheral perioperative stress is translated into sustained postoperative brain dysfunction remain incompletely understood. Extracellular vesicles (EVs) have attracted increasing attention in this context. As lipid bilayer-enclosed particles carrying proteins, lipids, and nucleic acids, EVs are involved in intercellular and inter-organ communication and may provide a mechanistic link between surgical injury and downstream cerebral responses. Emerging evidence suggests that EV-associated signals may participate in the progression from peripheral inflammation and vascular stress to blood-brain barrier dysfunction, neuroinflammation, complement-related synaptic injury, and neuronal dysfunction. In parallel, EV-associated cargo may offer a biologically informative peripheral signal for perioperative studies. This review summarizes the biological basis of EV signalling, major methodological issues relevant to EV research, and current clinical and experimental evidence linking EV-associated signals to PND. It also discusses source-specific EV populations and their potential relevance to perioperative brain injury.
Schwann cell derived extracellular vesicles (SC-EVs) have emerged as a specialized extracellular vesicle subtype with intrinsic neuroregenerative, neuroimmune, and neurovascular regulatory capacities, making them particularly relevant for diabetic oral mucosal wound healing. Unlike more widely studied extracellular vesicles derived from mesenchymal stem cells, SC-EVs originate from the principal glial cells of the peripheral nervous system and therefore retain biological programs directly related to axonal repair, neurotrophic support, and nerve-associated tissue regeneration. Diabetic oral mucosal wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, extracellular matrix dysregulation, and neuropathy-associated defects in epithelial repair. SC-EVs contain a distinctive cargo of proteins, RNAs, and lipids, including neurotrophic factors such as nerve growth factor and brain-derived neurotrophic factor, regulatory microRNAs such as miR-21 and miR-146a, and antioxidant molecules that collectively modulate these pathological processes. This review first summarizes the pathophysiological features of diabetic oral mucosal wounds, with emphasis on neurovascular and neuroimmune disruption. It then discusses the biogenesis, molecular composition, and functional mechanisms of SC-EVs, highlighting their roles in inflammatory recalibration, angiogenesis, neuroregeneration, and redox homeostasis. A dedicated discussion of SC-EV-specific cargo composition is included to clarify why SC-EVs represent a particularly suitable extracellular vesicle source for neuropathy-associated oral wound repair. Finally, we evaluate current progress in scalable production, targeted engineering, and biomaterial-assisted delivery, while outlining remaining limitations related to standardization, potency assessment, long-term safety, and clinical translation. By integrating glial biology with extracellular vesicle nanomedicine, this review provides a focused framework for developing SC-EV-based therapeutics for diabetic oral mucosal lesions.