Search Results (27)

Ischemic stroke remains a major cause of mortality and long-term disability, yet current therapeutic strategies are largely limited to reperfusion approaches such as intravenous thrombolysis and thrombectomy, which are constrained by narrow treatment windows and the risk of complications. Moreover, the blood–brain barrier (BBB) severely restricts drug penetration into the injured brain, limiting the translation of promising neuroprotective agents into clinical success. Intranasal (IN) delivery has emerged as a compelling alternative route that bypasses the BBB and enables rapid access to the central nervous system through olfactory, trigeminal, and perivascular pathways. This narrative review highlights recent advances in preclinical research on IN therapeutics for ischemic stroke, ranging from small molecules and biologics to nucleic acids and cell-based therapies. Particular emphasis is placed on the application of nanotechnology, including extracellular vesicles, liposomes, and inorganic nanoparticles, which enhance drug stability, targeting, and bioavailability. Studies demonstrate that IN delivery of growth factors, cytokines, and engineered stem cells can promote neurogenesis, angiogenesis, white matter repair, and functional recovery, while nanocarriers further expand the therapeutic potential. Overall, intranasal delivery represents a promising and non-invasive strategy to overcome the limitations of conventional stroke therapies, offering new avenues for neuroprotection and regeneration that warrant further investigation toward clinical translation. Full article

Glioblastoma is an aggressive and prevalent form of brain cancer characterized by rapid tumor cell migration and invasion into surrounding healthy tissues, making it resistant to conventional treatments. Despite advances in therapeutic approaches, patient prognosis remains poor, with a median survival of approximately 15 months. Tumor cell infiltration along perivascular spaces and white matter tracts is a major driver of recurrence, underscoring the need for experimental models that accurately capture these invasive behaviors. Animal models remain indispensable for this purpose, offering insights that cannot be fully replicated in vitro. This review focuses on applying animal models to elucidate the mechanisms underlying glioblastoma cell migration and invasion, which remain critical to improving therapeutic outcomes. By comparing the advantages of animal models with in vitro systems, we highlight the unique insights animal models provide, particularly in capturing the intricate dynamics of tumor cell motility. In particular, patient-derived xenograft (PDX) models preserve patient-specific heterogeneity and invasion patterns, such as white matter tract and perivascular infiltration, enabling clinically relevant drug testing. Zebrafish xenografts provide real-time, high-resolution visualization of tumor-vascular interactions, facilitating rapid assessment of invasion dynamics and early-stage drug screening. Genetically engineered models (GEM) allow precise discrimination of how defined genetic alterations drive specific invasive routes in the brain. Furthermore, we explore the use of advanced imaging techniques in these models to monitor tumor progression in real time. Moreover, we discuss the major drawbacks of these animal models, such as incomplete immune components and tumor microenvironment recapitulation. Ultimately, animal models are essential for bridging the gap between basic research and clinical application, offering a powerful platform for developing targeted strategies to combat glioblastoma’s relentless progression. Full article

Pericytes (PCs), a heterogeneous population of perivascular supporting cells, are critical regulators of vascular stability, angiogenesis, and blood–tissue barrier integrity. Increasing evidence highlights their active role in the pathophysiology of diabetic microangiopathies, including those affecting the retina, kidney, brain, heart, and peripheral nerves. In diabetes, hyperglycemia-induced PC dysfunction is a major contributor to vascular degeneration, impaired tissue repair, and disease progression across multiple organs. Pericytes also share many characteristics with mesenchymal stem cells (MSCs). They exhibit regenerative capacity, immunomodulatory activities, and multipotent capacities. This review explores the emerging role of PCs as tissue resident MSCs, emphasizing their pathophysiological involvement in diabetes complications, and their potential for utilization in regenerative medicine. We also discuss advances in PC-based therapies, tissue engineering strategies, and clinical applications. Thus, PCs are positioned as promising targets for therapeutic intervention and vascular tissue regeneration. Full article

Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article

Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors including PPAR-gamma and C/EBP alpha, while dysregulated adipogenesis can predispose adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that Cthrc1-null mice have increased adiposity compared to wildtype mice, supporting the notion that CTHRC1 regulates body composition. Herein, we derived conditioned medium from 3T3-L1 cells expressing human CTHRC1 and investigated its anti-adipogenic activity. This constituent significantly reduced 3T3-L1 cell adipogenic differentiation commensurate to the marked suppression of Cebpa and Pparg gene expression. It also increased the expression of the anti-adipogenic transcription factor SOX9 and promoted its nuclear translocation. Importantly, Sox9 gene knockdown demonstrated that the anti-adipogenic effect produced by this conditioned medium is dependent on SOX9 expression, while its ability to positively regulate SOX9 was attenuated by the application of Rho and Rac1 signaling pathway inhibitors. We also identified the selective expression of CTHRC1 in PDGFRA-expressing cell populations in human white adipose tissue, but not brown or perivascular adipose tissues. Congruently, flow cytometry revealed CTHRC1 expression in PDGFR-alpha⁺ stromal cells of mouse white adipose tissue, thus defining a novel stromal cell population that could underpin the ability of CTHRC1 to regulate adiposity. Full article

Magnetic resonance imaging (MRI) currently serves as the primary diagnostic method for glioma detection and monitoring. The integration of neurosurgery, radiation therapy, pathology, and radiology in a multi-disciplinary approach has significantly advanced its diagnosis and treatment. However, the prognosis remains unfavorable due to treatment resistance, inconsistent response rates, and high recurrence rates after surgery. These factors are closely associated with the complex molecular characteristics of the tumors, the internal heterogeneity, and the relevant external microenvironment. The complete removal of gliomas presents challenges due to their infiltrative growth pattern along the white matter fibers and perivascular space. Therefore, it is crucial to comprehensively understand the molecular features of gliomas and analyze the internal tumor heterogeneity in order to accurately characterize and quantify the tumor invasion range. The multi-parameter quantitative MRI technique provides an opportunity to investigate the microenvironment and aggressiveness of glioma tumors at the cellular, blood perfusion, and cerebrovascular response levels. Therefore, this review examines the current applications of advanced multi-parameter quantitative MRI in glioma research and explores the prospects for future development. Full article

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases. Full article

The perivascular space has been proposed as a clearance pathway for degradation products in the brain, including amyloid β, the accumulation of which may induce Alzheimer’s disease. Live images were acquired using a two-photon microscope through a closed cranial window in mice. In topical application experiments, the dynamics of FITC-dextran were evaluated from 30 to 150 min after the application and closure of the window. In continuous injection experiments, image acquisition began before the continuous injection of FITC-dextran. The transport of dextran molecules of different sizes was evaluated. In topical application experiments, circumferential accumulation around the penetrating arteries, veins, and capillaries was observed, even at the beginning of the observation period. No further increases were detected. In continuous injection experiments, a time-dependent increase in the fluorescence intensity was observed around the penetrating arteries and veins. Lower-molecular-weight dextran was transported more rapidly than higher-molecular-weight dextran, especially around the arteries. The largest dextran molecules were not transported significantly during the observation period. The size-dependent transport of dextran observed in the present study strongly suggests that diffusion is the main mechanism mediating substance transport in the perivascular space. Full article

Pericytes, as perivascular cells, are present in all vascularized organs and tissues, and they actively interact with endothelial cells in capillaries and microvessels. Their involvement includes functions like blood pressure regulation, tissue regeneration, and scarring. Studies have confirmed that pericytes play a crucial role in bone tissue regeneration through direct osteodifferentiation processes, paracrine actions, and vascularization. Recent preclinical and clinical experiments have shown that combining perivascular cells with osteogenic factors and tissue-engineered scaffolds can be therapeutically effective in restoring bone defects. This approach holds promise for addressing bone-related medical conditions. In this review, we have emphasized the characteristics of pericytes and their involvement in angiogenesis and osteogenesis. Furthermore, we have explored recent advancements in the use of pericytes in preclinical and clinical investigations, indicating their potential as a therapeutic resource in clinical applications. Full article

Nanofat is a relatively novel technique in fat grafting that has gained significant interest in the fields of regenerative medicine, aesthetic and translational research. It involves the extraction of autologous fat from a patient, which is then transformed into “nanofat”, consisting of small fat particles with a diameter of less than 0.1 mm and containing high concentrations of stem cells and growth factors. This article focuses on the use of nanofat in facial rejuvenation and its potential for lipomodelling. Fat tissue is a “stem cell depot” and nanofat contains many stem cells that can differentiate into various cell types. The Lipogem technology, developed in 2013, enables the isolation of nanofat with an intact perivascular structure, utilizing the high concentration of mesenchymal stromal cells near the pericytes of the adipose vascular system. Nowadays nanofat is used primarily for cosmetic purposes particularly in rejuvenating and improving the appearance of the skin, especially the face. Indeed, it has wide applicability; it can be used to treat fine lines, wrinkles, acne scars, sun-damaged skin, scar repair, and as an alopecia treatment. However, further studies are needed to assess the long-term efficacy and safety of this technique. In conclusion, nanofat is a safe and minimally invasive option for tissue regeneration with considerable therapeutic potential. This study reviews the application and effects of nanofat in regenerative medicine and facial cosmetic surgery. Full article

Dedifferentiated vascular smooth muscle cells (vSMCs) play an essential role in neointima formation, and we now aim to investigate the role of the bone morphogenetic protein (BMP) modulator BMPER (BMP endothelial cell precursor-derived regulator) in neointima formation. To assess BMPER expression in arterial restenosis, we used a mouse carotid ligation model with perivascular cuff placement. Overall BMPER expression after vessel injury was increased; however, expression in the tunica media was decreased compared to untreated control. Consistently, BMPER expression was decreased in proliferative, dedifferentiated vSMC in vitro. C57BL/6_Bmper+/− mice displayed increased neointima formation 21 days after carotid ligation and enhanced expression of Col3A1, MMP2, and MMP9. Silencing of BMPER increased the proliferation and migration capacity of primary vSMCs, as well as reduced contractibility and expression of contractile markers, whereas stimulation with recombinant BMPER protein had the opposite effect. Mechanistically, we showed that BMPER binds insulin-like growth factor-binding protein 4 (IGFBP4), resulting in the modulation of IGF signaling. Furthermore, perivascular application of recombinant BMPER protein prevented neointima formation and ECM deposition in C57BL/6N mice after carotid ligation. Our data demonstrate that BMPER stimulation causes a contractile vSMC phenotype and suggest that BMPER has the potential for a future therapeutic agent in occlusive cardiovascular diseases. Full article

Tissue organoids hold enormous potential as tools for a variety of applications, including disease modeling and drug screening. To effectively mimic the native tissue environment, it is critical to integrate a microvasculature with the parenchyma and stroma. In addition to providing a means to physiologically perfuse the organoids, the microvasculature also contributes to the cellular dynamics of the tissue model via the cells of the perivascular niche, thereby further modulating tissue function. In this review, we discuss current and developing strategies for vascularizing organoids, consider tissue-specific vascularization approaches, discuss the importance of perfusion, and provide perspectives on the state of the field. Full article

Intimal hyperplasia (IH) is an undesirable pathology occurring after peripheral or coronary bypass surgery. It involves the proliferation and migration of vascular smooth muscle cells, leading to a reduction in the diameter of the vascular lumen, which can lead to stenosis and graft failure. Topically applied atorvastatin (ATV) has been shown to slow down this process. To be effective, the drug delivery system should remain at the perivascular site for 5–8 weeks, corresponding to the progression of IH, and be capable of releasing an initial dose of the drug followed by a sustained release. Ideally, bioadhesion would anchor the gel to the application site. To meet these needs, we encapsulated ATV in a 2-component system: a hyaluronic acid–dopamine bioadhesive gel for rapid release and biodegradable microparticles for sustained release. The system was characterized by scanning electron microscopy, rheology, bioadhesion on porcine arteries, and a release profile. The rheological properties were adequate for perivascular application, and we demonstrated superior bioadhesion and cohesion compared to the control HA formulations. The release profile showed a burst, generated by free ATV, followed by sustained release over 8 weeks. A preliminary evaluation of subcutaneous biocompatibility in rats showed good tolerance of the gel. These results offer new perspectives on the perivascular application towards an effective solution for the prevention of IH. Full article

The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials. Full article

This study reports new phenomena of the interstitial fluid (ISF) microflow along perivascular and adventitial clearances (PAC) around neurovascular bundles. The fluorescent tracing was used to observe the ISF flow along the PAC of neurovascular bundles in 8–10 week old BALB/c mice. The new results include: (1) the topologic structure of the PAC around the neurovascular bundles is revealed; (2) the heart-orientated ISF flow along the PAC is observed; (3) the double-belt ISF flow along the venous adventitial clearance of the PAC is recorded; (4) the waterfall-like ISF flow induced by the small branching vessel or torn fascia along the PAC is discovered. Based on the above new phenomena, this paper approached the following objectives: (1) the kinematic laws of the ISF flow along the PAC around neurovascular bundles are set up; (2) the applicability of the hypothesis on the PAC and its subspaces by numerical simulations are examined. The findings of this paper not only enriched the image of the ISF flow through the body but also explained the kernel structure of the ISF flow (i.e., the PAC). It helps to lay the foundation for the kinematics and dynamics of the ISF flow along the PAC around neurovascular bundles. Full article