Biology subjects

Ferrarese, C.

Publications and source records attributed to Ferrarese, C..

3 recordsLinked to original sources

bioRxiv2025

Multi-center Translational Trial of Remote Ischemic Conditioning in Acute Ischemic Stroke (TRICS BASIC)

BackgroundBasic science studies have reported remote ischemic conditioning (RIC) as neuroprotective in acute ischemic stroke, while clinical evidence remains conflicting. The TRICS BASIC study investigated the efficacy and safety of RIC in experimental ischemic stroke using a rigorous clinical trial methodology. MethodsMulti-center, multi-species, parallel group, randomized, controlled, preclinical trial of transient femoral artery clipping to induce RIC in female and male rats and mice subjected to transient endovascular occlusion of the middle cerebral artery. Animals were randomized to receive RIC, or sham surgery, after reperfusion. The primary endpoint was good functional outcome at 48 hours, assessed using a composite functional neuroscore. Secondary endpoints was infarct volume at 48 hours and safety, assessed using a standardized health report at 24 and 48 hours. Pre-enrollment harmonization, centralized monitoring, allocation concealment, blinded outcome assessment and intention-to-treat analysis were applied. ResultsThe trial enrolled 164 rodents (82 mice and 82 rats) of both sexes (53% females), across seven laboratories. A greater proportion of RIC-treated rodents achieved a favorable functional outcome compared to controls, at 48 hours post-ischemia (55% versus 36%; OR 2.2, 95% CI [1.23-4.4], p=0.009). RIC was associated with a small reduction in infarct volume (standardized mean difference -0.38, 95% CI [-0.70, -0.05], p=0.024). Health monitoring indicated no major safety concerns, and post-operative analgesia requirements were lower in RIC-treated mice. ConclusionsSurgically-induced RIC provided a modest but evident neuroprotective effect in experimental ischemic stroke, underscoring the potential of this strategy as an adjunctive treatment in stroke care. The findings of the TRICS BASIC study highlighted the importance of multicenter preclinical trials in addressing variability and enhancing translational validity. Registrationregistered at preclinicaltrials.eu, identifier PCTE0000177.

neuroscience↗

bioRxiv2024

Head down tilt 15° increases cerebral perfusion before recanalization in acute ischemic stroke: a pre-clinical MRI study.

We investigated the therapeutic effect of head down positioning at -15{degrees} (head down tilt; HDT15) on cerebral collateral flow and infarct growth in a rat model of large vessel occlusion (LVO) stroke, using multi-modal MRI. Twenty-eight Wistar rats were randomly assigned to HDT15 or flat position for 60 minutes, starting 30 minutes after occlusion of the middle cerebral artery, followed by reperfusion. The perfusion shift analysis, comparing post- versus pre-treatment voxel-level changes in time-to-peak perfusion maps, showed a significant increase in cerebral perfusion in the HDT15 group (common odds ratio 1.50; 95% CI 1.41-1.60; p < 0.0001), but not in the flat group (common odds ratio 0.97; 95% CI 0.92-1.03; p = 0.3503). Infarct growth at 24 hours was + 31.4% in the flat group (343 versus 250 mm3; 95% CI 2.4 to 165.1; p = 0.0447) and + 15.4% in the HDT15 group (224 versus 192 mm3; 95% CI -26.9 to 85.9; p = 0.2272). Our findings indicate that HDT15 acutely increases cerebral perfusion in LVO acute ischemic stroke and provides a tissue-saving effect before recanalization. Further research is needed to develop HDT15 as an emergency therapy to acutely increase collateral flow in ischemic stroke prior to recanalization therapy.

neuroscience↗

bioRxiv2018

Stavudine Reduces NLRP3-Inflammasome Activation and Upregulates Aβ-Autophagy

Alzheimers disease (AD) is associated with amyloid-beta (A{beta}) deposition and neuroinflammation, possibly driven by activation of the NLRP3 inflammasome. Nucleoside reverse transcriptase inhibitors (NRTI) hamper the assembly of the NLRP3 inflammasome; we analyzed whether stavudine (D4T), a prototypical NRTI, modulates A{beta}-mediated inflammasome activation; because neuroinflammation impairs A{beta} clearance by phagocytes, phagocytosis and autophagy were examined as well. THP-1-derived macrophages were stimulated in vitro with A{beta}42 alone or after LPS priming with/without D4T. NLRP3 and TREM2 expression was analyzed by RT-PCR, phagocytosis and ASC-Speck by AmnisFlowSight, NLRP3-produced cytokines by ELISA, authophagy by P-ELISA evaluation of P-ERK and P-AKT. Results showed that IL1{beta}, IL18 and caspase-1 were increased whereas A{beta}-phagocytosis and TREM2 were reduced in LPS+A{beta}42-stimulated cells. D4T reduced NLRP3 assembly as well as IL18 and caspase-1 production, but not IL1{beta}, phagocytosis, and TREM2. P-AKT expression was augmented and P-ERK was reduced by D4T, suggesting a stimulatory effect on autophagy. D4T reduces NLRP3 inflammasome-associated inflammation, possibly restoring autophagy, in an in vitro model of AD; it will be interesting to verify its possibly beneficial effects in the clinical scenario.

molecular biology↗