Dual role of vascular endothelial growth factor-C in post-stroke recovery DOI
Yun Hwa Choi, Martin Hsu, Collin Laaker

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 222(2)

Published: Dec. 12, 2024

Cerebrospinal fluid (CSF), antigens, and antigen-presenting cells drain from the central nervous system (CNS) into lymphatic vessels near cribriform plate dura, yet role of these during stroke is unclear. Using a mouse model ischemic stroke, transient middle cerebral artery occlusion (tMCAO), we demonstrate stroke-induced lymphangiogenesis plate, peaking at day 7 regressing by 14. Lymphangiogenesis restricted to deep cervical lymph nodes regulated VEGF-C/VEGFR-3 signaling. The use VEGFR-3 inhibitor prevented led improved outcomes earlier time points, with no effects later points. VEGF-C delivery after tMCAO did not further increase post-stroke lymphangiogenesis, but instead induced larger brain infarcts. Our data support damaging acutely pro-angiogenic chronically. This nuanced understanding in pathology advises caution regarding therapeutic stroke.

Language: Английский

Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer’s disease-related amyloid pathology DOI Creative Commons
Salli Antila, Dmitri Chilov, Harri Nurmi

et al.

Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(4), P. 474 - 491

Published: March 15, 2024

Abstract Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest their possible involvement Alzheimer’s disease (AD). Here we find APdE9 and 5xFAD mouse models AD, amyloid-β (Aβ) is confined to blood dLV morphology or function not altered. The induction sustained atrophy hyperplasia AD mice by blocking overexpressing C, impaired improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage cervical lymph nodes. Yet, manipulation dLVs did significantly alter overall brain Aβ plaque load. Moreover, behavioral phenotypes mice, but it improved CSF-to-blood drainage. Our results indicate does affect deposition compensatory mechanisms promote CSF clearance.

Language: Английский

Citations

16
Meningeal lymphatics-microglia axis regulates synaptic physiology DOI Creative Commons
Kyungdeok Kim,

Daviti Abramishvili,

Siling Du

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

3
The Role of Platelet-Rich Plasma in Biomedicine: A Comprehensive Overview DOI Creative Commons
Zhixin Zhang, Peng Liu,

Xinmiao Xue

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111705 - 111705

Published: Jan. 5, 2025

Biomedicine has seen significant advancements in the 21st century, with platelet-rich plasma (PRP) playing a crucial role clinical practice. This blood derivative, enriched platelet components, shown great potential for promoting tissue repair and regeneration. Its wide range of applications presence anti-inflammatory growth-promoting factors make it valuable tool field biomedicine. The exploration PRP settings been gaining momentum. Despite its cost-effectiveness, safety, therapeutic efficacy, widespread adoption hindered by absence consistent preparation standards standardized treatment protocols. article provides comprehensive analysis uses, physiological roles, molecular mechanisms, techniques aim is to offer thorough understanding benefits medical

Language: Английский

Citations

2
The Impact of VEGF-C-Induced Dural Lymphatic Vessel Growth on Ischemic Stroke Pathology DOI Creative Commons
Meike Hedwig Keuters, Salli Antila, Riikka Immonen

et al.

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Timely relief of edema and clearance waste products, as well promotion anti-inflammatory immune responses, reduce ischemic stroke pathology, attenuate harmful long-term effects post-stroke. The discovery an extensive functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural (dLV) growth via a single injection vector encoding vascular endothelial factor C (VEGF-C). In present study, we aimed improve outcomes dLV mice. We injected mice with intracerebroventricular dose adeno-associated viral particles VEGF-C before subjecting them transient middle cerebral artery occlusion (tMCAo). Behavioral testing, Gadolinium (Gd) contrast agent-enhanced magnetic resonance imaging (MRI), immunohistochemical analysis were performed define impact on outcome. improved stroke-induced behavioral deficits, such gait disturbances neurological ameliorated inflammation, enhanced alternative glial response. Importantly, treatment increased drainage brain interstitial fluid (ISF) cerebrospinal (CSF), shown Gd-enhanced MRI. These closely associated increase dLVs around region where observed vefgc mRNA expression within brain, including olfactory bulb, cortex, cerebellum. Strikingly, VEGF-C-treated exhibited faster stronger Gd-signal accumulation core area outflow cribriform plate. conclusion, VEGF-C-induced overall outcome post-stroke, indicating that potential be included strategies post-ischemic stroke. However, maximize therapeutic treatment, further studies at clinically relevant time points are essential.

Language: Английский

Citations

4
Cerebral Venous Blood Flow Regulates Brain Fluid Clearance via Meningeal Lymphatics DOI Creative Commons

Marie-Rénée El Kamouh,

Myriam Spajer, Ruchith Singhabahu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract The vascular system regulates brain clearance through arterial blood flow and lymphatic drainage of cerebrospinal fluid (CSF). Idiopathic intracranial hypertension (IIH), characterized by elevated pressure dural venous sinus stenoses, can be treated restoring via stenting, suggesting a role for in clearance. Using magnetic resonance imaging (MRI) IIH patients healthy controls, we identified that stenoses were associated with impaired drainage, perivenous retention, accumulation. To investigate this further, developed mouse model bilateral jugular vein ligation (JVL), which recapitulated key human findings, including hypertension, calvarial regression, swelling due to further dissect the respective roles meningeal vessels clearance, performed JVL mice depletion. These exhibited spontaneous pressure, but did not exacerbate effect. Moreover, synchronous restoration lymphatics observed after was absent lymphatic-deficient mice.Transcriptomic analyses revealed remodeling induced driven VEGF-C signaling between mesenchymal endothelial cells. findings establish sinuses as critical platform where interacts cells preserve integrity function, essential

Language: Английский

Citations

0
Molecular Regulation and Therapeutic Applications of Brain-Derived Neurotrophic Factor–Tropomyosin-Related Kinase B Signaling in Major Depressive Disorder Though Its Interaction with Vascular Endothelial Growth Factor and N-Methyl-D-Aspartic Acid Receptors: A Narrative Review DOI Creative Commons

Yasunari Matsuzaka,

Ryu Yashiro

Biologics, Journal Year: 2025, Volume and Issue: 5(1), P. 7 - 7

Published: March 3, 2025

The molecular regulation and therapeutic applications of brain-derived neurotrophic factor (BDNF)–tropomyosin-related kinase B (TrkB) signaling in major depressive disorder (MDD) through interaction with vascular endothelial growth (VEGF) N-methyl-D-aspartic acid (NMDA) receptors show promise. While BDNF-TrkB is implicated antidepressant action, the association between BDNFs depression has not yielded conclusive results. Some studies decreased BDNF levels depression, while others indicate that increased expression certain brain regions can induce susceptibility. role varies across different regions, necessitating further study individual mechanisms. This regional variability complicates development targeted therapies. antidepressant-like actions require VEGF signaling, but there also a reciprocal interdependence, as are dependent on BDNFs. complex relationship

Language: Английский

Citations

0
Glymphatic system dysfunction and cerebrospinal fluid retention in gliomas: evidence from perivascular space diffusion and volumetric analysis DOI Creative Commons

Weiqiang Liang,

Wenbo Sun, Chunyan Li

et al.

Cancer Imaging, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 7, 2025

Abstract Background Gliomas may impair glymphatic function and alter cerebrospinal fluid (CSF) dynamics through structural brain changes, potentially affecting peritumoral edema (PTBE) clearance. This study investigated the impact of gliomas on system CSF volume via diffusion tensor imaging analysis along perivascular space (DTI-ALPS) volumetric magnetic resonance (MRI), which clarified relationships between tumor characteristics disruption. Methods In this prospective study, 112 glioma patients 56 healthy controls underwent MRI to calculate DTI-ALPS indices perform analyses CSF, tumor, PTBE. Statistical were used assess index, volume, PTBE clinical characteristics. Results Glioma had significantly lower (1.266 ± 0.258 vs. 1.395 0.174, p < 0.001) greater volumes (174.53 34.89 cm³ 154.25 20.89 cm³, than did. The index was inversely correlated with ( r = -0.353, -0.266, 0.015). High-grade associated larger (all 0.001). Tumor grade emerged as an independent predictor in multivariate (β -0.244, 0.011). Conclusion are significant dysfunction, evidenced by reduced increased volumes. serves a potential biomarker disruption patients, offering insights into tumor-related changes pathophysiology brain-tumor interactions.

Language: Английский

Citations

0
Liver Lymphatic Dysfunction as a Driver of Fibrosis and Cirrhosis Progression DOI Open Access

Jain Jeong,

Shao‐Jung Hsu, Daiki Horikami

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract The liver lymphatic system plays a critical role in maintaining interstitial fluid balance and immune regulation. Efficient drainage is essential for homeostasis, but its disease progression remains poorly understood. In cirrhosis, lymphangiogenesis initially compensates increased lymph production, impaired advanced stages may lead to complications such as ascites portal hypertension. This study aimed evaluate how dysfunction affects assess therapeutic strategies. Using surgical model block outflow, we found that accelerates injury, fibrosis, cell infiltration, even healthy livers. Mechanistically, enhanced TGF-β signaling endothelial cells (LyECs) contributed reduced vessel (LV) density function late-stage decompensated cirrhosis. was linked the from compensated particularly patients with primary sclerosing cholangitis (PSC). Conversely, liver-specific overexpression of VEGF-C via AAV8 improved drainage, restored LV density, mitigated alleviated hypertension cirrhotic rats. These findings establish pivotal driver cirrhosis identify promising target prevent decompensation.

Language: Английский

Citations

0
Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure DOI Creative Commons
Bahar Aksan, Daniela Mauceri

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: March 6, 2025

Neurons rely on the bloodstream for essential nutrients and oxygen, which is facilitated by an intricate coupling of neuronal vascular systems. Central to this neurovascular interaction endothelial growth factor (VEGF) family, a group secreted factors traditionally known their roles in promoting cell proliferation, migration, survival cardiovascular lymphatic However, emerging evidence shows that VEGFs also play indispensable nervous system, extending beyond canonical angiogenic lymphangiogenic functions. Over past two decades, have been found exert direct effects neurons, influencing key aspects function independently actions cells. In particular, it has become increasingly evident crucial functions development, regulation, maintenance morphology. Understanding development high scientific clinical interest because significance precise morphology neural connectivity network function, as well association morphological abnormalities with neurological neurodegenerative disorders. This review begins overview VEGF family members, structural characteristics, receptors, established vasculature. then highlights focuses exciting variety VEGFs, especially role

Language: Английский

Citations

0
Covert cerebrospinal fluid dynamics dysfunction: evolution from conventional to innovative therapies DOI Creative Commons
Yi Xu, Hua Yin, Lingge Li

et al.

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

Cerebrospinal fluid (CSF) dynamics disorders are intricately linked to diverse neurological pathologies, though they usually mild and covert. Contemporary insights into glymphatic system function, particularly the CSF transport, drainage, its role in clearing metabolic waste toxic substances both normal pathological states, pivotal of aquaporin-4 (AQP4) CSF-interstitial (ISF) exchange, have established novel theoretical frameworks subclinical dysfunction, promoted development non-surgical therapeutic approaches for them simultaneously. This review comprehensively analyzes advancement interventions disorders, emphasizing transition from methodologies innovative approaches. Current treatment strategies primarily encompass three directions: pharmacological therapy, physical biological regulation therapy. In terms interventions, developments traditional diuretics small-molecule drugs show promising potential. techniques such as lower body negative pressure, transcranial magnetic stimulation, vagus nerve stimulation provided new options clinical practice. Meanwhile, exemplified by recombinant VEGF-C administration, has paradigms. These demonstrated potential improving enhancing elimination. Future research should focus on developing individualized protocols, elucidating mechanisms, assessing longitudinal outcomes. will facilitate more precise exploration optimized multimodal combinations handling so-called convert dysfunction.

Language: Английский

Citations

0