The neurovascular unit and systemic biology in stroke – implications for translation and treatment

Tiedt S, Buchan AM, Dichgans M, Lizasoain I, Moro MA, Lo EH. Nat Rev Neurol. 2022 Sep 9. doi: 10.1038/s41582-022-00703-z. Online ahead of print. PMID: 36085420 

Abstract | Ischaemic stroke is a leading cause of disability and death for which no acute treatments exist beyond recanalization. The development of novel therapies has been repeatedly hindered by translational failures that have changed the way we think about tissue damage after stroke. What was initially a neuron-centric view has been replaced with the concept of the neurovascular unit (NVU), which encompasses neuronal, glial and vascular compartments, and the biphasic nature of neural–glial–vascular signalling. However, it is now clear that the brain is not the private niche it was traditionally thought to be and that the NVU interacts bidirectionally with systemic biology, such as systemic metabolism, the peripheral immune system and the gut microbiota. Furthermore, these interactions are profoundly modified by internal and external factors, such as ageing, temperature and day–night cycles. In this Review, we propose an extension of the concept of the NVU to include its dynamic interactions with systemic biology. We anticipate that this integrated view will lead to the identification of novel mechanisms of stroke pathophysiology, potentially explain previous translational failures, and improve stroke care by identifying new biomarkers of and treatment targets in stroke.

Unraveling the potential of endothelial progenitor cells as a treatment following ischemic stroke


Custodia A, Ouro A, Sargento-Freitas J, Aramburu-Núñez M et al. Front Neurol. 2022 Sep 8;13:940682. doi: 10.3389/fneur.2022.940682. eCollection 2022. PMID: 36158970
Abstract: After stroke and other brain injuries, there is a high incidence of respiratory complications such as pneumonia or acute lung injury. The molecular mechanisms that drive the brain-lung interaction post-stroke have not yet been elucidated. We performed transient middle cerebral artery
occlusion (MCAO) and sham surgery on C57BL/6J mice and collected bronchoalveolar lavage fluid (BALF), serum, brain, and lung homogenate samples 24 h after surgery. A 92 proteins-panel developed by Olink Proteomics® was used to analyze the content in BALF and lung homogenates. MCAO animals had higher protein concentration levels in BALF than sham-controls, but these levels did not correlate with the infarct volume. No alteration in alveolar-capillary barrier permeability was observed. A total of 12 and 14 proteins were differentially expressed between the groups (FDR < 0.1) in BALF and lung tissue homogenates, respectively. Of those, HGF, TGF-α, and CCL2 were identified as the most relevant to this study. Their protein expression patterns were verified by ELISA. This study confirmed that post-stroke lung damage was not associated with increased lung permeability or cerebral ischemia severity. Furthermore, the dysregulation of HGF, TGF-α, and CCL2 in BALF and lung tissue after ischemia could play an important role in the molecular mechanisms underlying stroke-induced lung damage.
Funding: This project received funding from Instituto de Salud Carlos III (ISCIII) [PI17/02130,PI21/00939], co-financed by the European Regional Development Fund (FEDER), from the Fundació La Marató de TV3 [201706]. The participating centers take part into RICORS-ICTUS network [RD21/0006/0024, RD21/0006/0007, RD21/0006/0015] from Instituto de Salud Carlos III (ISCIII) [PI17/02130, PI21/00939], co-financed by the European Regional Development Fund (FEDER). The funders had no role in designing or executing this study.

Detection of hidden atrial fibrillation in primary care using a long-term band-based ECG registration system: The DESCUUBRE-FA study

Ximénez-Carrillo Á, Zapata-Wainberg G, Sastre R, Álvarez-Pasquín MJ, Javierre AP, Lozano T, Samir E, Perosanz L, González B, Sobrado M, Vivancos J. J Stroke Cerebrovasc Dis. 2022 Sep;31(9):106642. doi: 10.1016/j.jstrokecerebrovasdis.2022.106642. Epub 2022 Jul 18. PMID: 35863263 

Objective: To assess whether the use of a band-based electrocardiographic (ECG) monitoring system improves the diagnostic accuracy of traditional diagnostic methods for the detection of atrial fibrillation (AF). Methods:Multicenter and observational study of primary care patients at risk of AF. To be included, patients had to be aged 70 years, with no known AF, and have at least 1 major criterion (obesity, hyperthyroidism, heart failure) or 2 minor criteria (hypertension, diabetes, female sex, ischemic stroke, transient ischemic attack or systemic embolism, COPD, dyslipidemia, ischemic heart disease, peripheral artery disease). All patients were monitored using the NuuboTM system for a single 2-week period. Results: A total of 600 patients were included (median age 77 years; 70% women; 84.3% hypertension, 27.2% diabetes, 9.2% prior stroke). The global rate of diagnosis of new AF in the overall population was 2.83%. All patients with AF were anticoagulated. In numerical terms, patients with AF (vs no AF) had a higher number of supraventricular extrasystoles and episodes of supraventricular tachycardia, as well as longer P wave duration; however, these differences did not reach statistical significance. Overall, participants were very satisfied with the device, and no relevant limitations in daily activities were observed during the 2-week study period. Conclusions: In an elderly population at risk of AF, a band-based ECG monitoring approach applied for only 2 weeks detected approximately 3% of new cases of AF, leading to a change in antithrombotic therapy. Most participants considered the device easy to use and comfortable.

This research has been financed by the Carlos III Health Institute (PI18/00361 and RICORS-RD21/0006/0009) and co-financed with ERDF Funds and/or charged to the European funds of the Recovery, Transformation and Resilience Plan and by the NextGenerationEU.