microvascular-embolism-mouse-model-for-vivo-two-photon-microscopy

Microvascular Embolism Mouse Model for <em>In Vivo</em> Two-photon Microscopy Using Fluorescent Polystyrene Microspheres

Microvascular occlusions in the brain are relatively common but remain largely understudied. The event rate, long-term consequences, and potential ...

University of Amsterdam

Amsterdam Neuroscience, neurovascular disorders

Amsterdam Cardiovascular Sciences

Minimally-invasive tools to assess tumour presence and burden may improve clinical management. FDG-PET (metabolic) imaging is the current gold standard for interim response assessment in patients with classical Hodgkin Lymphoma (cHL), but this technique cannot be repeated frequently. Here we show that microRNAs (miRNA) associated with tumour-secreted extracellular vesicles (EVs) in the circulation of cHL patients may improve response assessment. Small RNA sequencing and qRT-PCR reveal that the relative abundance of cHL-expressed miRNAs, miR-127-3p, miR-155-5p, miR-21-5p, miR-24-3p and let-7a-5p is up to hundred-fold increased in plasma EVs of cHL patients pre-treatment when compared to complete metabolic responders (CMR). Notably, in partial responders (PR) or treatment-refractory cases (= 10) the EV-miRNA levels remain elevated. In comparison, tumour specific copy number variations (CNV) were detected in cell-free DNA of 8 out of 10 newly diagnosed cHL patients but not in patients with PR. Combining EV-miR-127-3p and/or EV-let-7a-5p levels, with serum TARC (a validated protein cHL biomarker), increases the accuracy for predicting PET-status (= 129) to an area under the curve of 0.93 (CI: 0.87-0.99), 93.5% sensitivity, 83.8/85.0% specificity and a negative predictive value of 96%. Thus the level of tumour-associated miRNAs in plasma EVs is predictive of metabolic tumour activity in cHL patients. Our findings suggest that plasma EV-miRNA are useful for detection of small residual lesions and may be applied as serial response prediction tool.

Extracellular vesicle miRNA predict FDG-PET status in patients with classical Hodgkin Lymphoma.

Blood-brain barrier (BBB) dysfunction and immune cell migration into the central nervous system (CNS) are pathogenic drivers of multiple sclerosis (MS). Ways to reinstate BBB function and subsequently limit neuroinflammation present promising strategies to restrict disease progression. However, to date, the molecular players directing BBB impairment in MS remain poorly understood. One suggested candidate to impact BBB function is the transient receptor potential vanilloid-type 4 ion channel (TRPV4), but its specific role in MS pathogenesis remains unclear. Here, we investigated the role of TRPV4 in BBB dysfunction in MS.

Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.

The cerebral circulation is continuously challenged by intravascular micrometer-sized particles that become trapped microvascular-emboli. These particles may include micro-thrombi, stiffened erythrocytes, and leukocytes, while also fat particles, air, and microplastics may cause microvascular embolism.

Article	Year
Extracellular vesicle miRNA predict FDG-PET status in patients with classical Hodgkin Lymphoma. Journal of extracellular vesicles\| PubMed ID: 34295456	2021
Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis. Journal of neuroinflammation\| PubMed ID: 38521959	2024
Micro-Embolic Events and Their Clearing in the Brain. A Narrative Review. Acta physiologica (Oxford, England)\| PubMed ID: 40928049	2025

Kevin Mol

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