Brain hypothermia in ischemic stroke: non-invasive thermometry and molecular basis

Ischemic stroke is a leading cause of death and morbidity around the world. However, only one pharmacological treatment is currently available, the tissue plasminogen activator or rtPA. Preclinical studies demonstrated the high therapeutic potential of hypothermia to mitigate the effects of stroke, but this therapy has not been successfully translated to the clinics due to the side effects associated to cold (shivering, arrhythmia, or pneumonia among others), and due to the lack of non-invasive methods to assess brain temperature. The present work provides new data about the therapeutic potential of focal brain hypothermia as alternative to systemic cooling, the use of non-invasive magnetic resonance thermometry to measure brain temperature, and the possible implication of RBM3, a cold shock protein, in the molecular process underlying the protective effect of cold

Hyperthermia in human ischemic and hemorrhagic stroke: similar outcome, different mechanisms

Hyperthermia is a predictor of poor outcome in ischemic (IS) and intracerebral hemorrhagic (ICH) stroke. Our aim was to study the plausible mechanisms involved in the poor outcome associated to hyperthermia in stroke. We conducted a case-control study including patients with IS (n = 100) and ICH (n = 100) within the first 12 hours from symptom onset. Specifically, IS and ICH patients were consecutively included into 2 subgroups, according to the highest body temperature within the first 24 hours: Tmax 2) at 3 months. Serum levels of glutamate and active MMP-9 were measured at admission. Our results showed that Tmax ≥37.5°C within the first 24 hours was independently associated with poor outcome in both IS (OR, 12.43; 95% CI, 3.73-41.48; p<0.0001) and ICH (OR, 4.29; 95% CI, 1.32-13.91; p = 0.015) after adjusting for variables with a proven biological relevance for outcome. However, when molecular markers levels were included in the logistic regression model, we observed that glutamate (OR, 1.01; 95% CI, 1.00-1.02; p = 0.001) and infarct volume (OR, 1.06; 95% CI, 1.01-1.10; p = 0.015) were the only variables independently associated to poor outcome in IS, and active MMP-9 (OR, 1.04; 95% CI, 1.00-1.08; p = 0.002) and National Institute of Health Stroke Scale (NIHSS) at admission (OR, 1.29; 95% CI, 1.13-1.49; p<0.0001) in ICH. In conclusion, these results suggest that although the outcome associated to hyperthermia is similar in human IS and ICH, the underlying mechanisms may be different

Higher expression of Toll-like receptors 2 and 4 in blood cells of Keratoconus patiens

Inflammation may play a significant role in Keratoconus (KC), but the implication of immunity on this inflammatory response is unknown. Therefore, our aim was to determine the expression levels of Toll-like receptors 2 (TLR2) and 4 (TLR4) in monocytes and neutrophils from patients with KC and control subjects for demonstrating the role of innate immunity in KC. We also study the correlation between TLR2/TLR4 expression and serum levels of proinflammatory markers (IL-1β, IL-6, TNF-α, MMP-9 and NF-κB). Forty patients with bilateral KC (55% males; mean age; 33.1 ± 10.9 years) and 20 control subjects (55% males; mean age; 30.4 ± 7.6 years) were included in the study. Our results showed that mean expression of TLR2 and TLR4 in both neutrophils and monocytes was significantly higher in patients with KC compared to control subjects (all p < 0.0001). Furthermore, KC patients also showed higher serum levels of IL-1B, IL-6, TNF-α, MMP-9 (all p < 0.0001) and NF-κB (p = 0.036). In addition, we found a strong correlation between TLR2 expression in both monocytes and neutrophils (all p < 0.0001), and TLR4 in monocytes (all p < 0.05) with serum levels of IL-1B, IL-6, TNF-α and MMP-9. In conclusion, these findings suggest that TLRs may play an important role in the pathophysiology of KC.This project has been supported by grants from the Spanish Ministry of Economy and Competitiveness (Instituto de Salud Carlos III: PI14/00247); Xunta de Galicia (Consellería de Economía e Industria: 10 PX113918156PR and Consellería de Educación: GRC2014/027) and the European Union program FEDER. T. Sobrino (CP12/03121) and F. Campos (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III. Likewise A. Vieites-Prado is recipient of a FPI fellow (BES-2012-056027) from the Spanish Ministry of Economy and Competitiveness; and U. Regueiro is recipient of a predoctoral Fellow from the Xunta de Galicia (ED481A-2015/001)S

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.This study has been partially supported by grants from Axencia Galega de Innovación (Xunta de Galicia), the Instituto de Salud Carlos III (PI13/00292; PI14/01879), the Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS (RD12/0014), Xunta de Galicia (Consellería Educación GRC2014/027), the European Commission program FEDER and Promoting Active Ageing program: Functional Nanostructures For Alzheimer’s Disease At Ultra-Early Stages” (Pana_686009), a Research and Innovation Project, funded within the EU Horizon 2020 Programme”. Furthermore, this study was also co-funded within the POCTEP (Operational Programme for Cross-border Cooperation Spain-Portugal) program (0681_INVENNTA_1_E), co-financed by the ERDF (European Regional Development Fund). T. Sobrino (CP12/03121) and F. Campos (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III. Finally, P. Taboada thanks Mineco and Xunta de Galicia for funding through projects MAT2013-40971-R and EM2013-046, respectively. J Trekker is the recipient of an innovation grant from the IWT-VlaanderenS

Author Correction: Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants.

International audienceNo abstract availabl

Tissue clearing and 3D imaging in developmental biology

International audienceTissue clearing increases the transparency of late developmental stages and enables deep imaging in fixed organisms. Successful implementation of these methodologies requires a good grasp of sample processing, imaging and the possibilities offered by image analysis. In this Primer, we highlight how tissue clearing can revolutionize the histological analysis of developmental processes and we advise on how to implement effective clearing protocols, imaging strategies and analysis methods for developmental biology