Francesca Motta

Scopus Publications

Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect
Giulia Merigo, Gaetano Florio, Fabiana Madotto, Aurora Magliocca, Ivan Silvestri, Francesca Fumagalli, Marianna Cerrato, Francesca Motta, Daria De Giorgio, Mauro Panigada,et al.
Elsevier BV

Indoleamine 2,3-Dioxygenase Deletion to Modulate Kynurenine Pathway and to Prevent Brain Injury after Cardiac Arrest in Mice
Aurora Magliocca, Carlo Perego, Francesca Motta, Giulia Merigo, Edoardo Micotti, Davide Olivari, Francesca Fumagalli, Jacopo Lucchetti, Marco Gobbi, Alessandra Mandelli,et al.
Ovid Technologies (Wolters Kluwer Health)
Background The catabolism of the essential amino acid tryptophan to kynurenine is emerging as a potential key pathway involved in post–cardiac arrest brain injury. The aim of this study was to evaluate the effects of the modulation of kynurenine pathway on cardiac arrest outcome through genetic deletion of the rate-limiting enzyme of the pathway, indoleamine 2,3-dioxygenase. Methods Wild-type and indoleamine 2,3-dioxygenase–deleted (IDO−/−) mice were subjected to 8-min cardiac arrest. Survival, neurologic outcome, and locomotor activity were evaluated after resuscitation. Brain magnetic resonance imaging with diffusion tensor and diffusion-weighted imaging sequences was performed, together with microglia and macrophage activation and neurofilament light chain measurements. Results IDO−/− mice showed higher survival compared to wild-type mice (IDO−/− 11 of 16, wild-type 6 of 16, log-rank P = 0.036). Neurologic function was higher in IDO−/− mice than in wild-type mice after cardiac arrest (IDO−/− 9 ± 1, wild-type 7 ± 1, P = 0.012, n = 16). Indoleamine 2,3-dioxygenase deletion preserved locomotor function while maintaining physiologic circadian rhythm after cardiac arrest. Brain magnetic resonance imaging with diffusion tensor imaging showed an increase in mean fractional anisotropy in the corpus callosum (IDO−/− 0.68 ± 0.01, wild-type 0.65 ± 0.01, P = 0.010, n = 4 to 5) and in the external capsule (IDO−/− 0.47 ± 0.01, wild-type 0.45 ± 0.01, P = 0.006, n = 4 to 5) in IDO−/− mice compared with wild-type ones. Increased release of neurofilament light chain was observed in wild-type mice compared to IDO−/− (median concentrations [interquartile range], pg/mL: wild-type 1,138 [678 to 1,384]; IDO−/− 267 [157 to 550]; P &lt; 0.001, n = 3 to 4). Brain magnetic resonance imaging with diffusion-weighted imaging revealed restriction of water diffusivity 24 h after cardiac arrest in wild-type mice; indoleamine 2,3-dioxygenase deletion prevented water diffusion abnormalities, which was reverted in IDO−/− mice receiving l-kynurenine (apparent diffusion coefficient, μm2/ms: wild-type, 0.48 ± 0.07; IDO−/−, 0.59 ± 0.02; IDO−/− and l-kynurenine, 0.47 ± 0.08; P = 0.007, n = 6). Conclusions The kynurenine pathway represents a novel target to prevent post–cardiac arrest brain injury. The neuroprotective effects of indoleamine 2,3-dioxygenase deletion were associated with preservation of brain white matter microintegrity and with reduction of cerebral cytotoxic edema. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Characterization of the Cardiac Structure and Function of Conscious D2.B10-Dmd<sup>mdx</sup>/J (D2-mdx) mice from 16–17 to 24–25 Weeks of Age
Daria De Giorgio, Deborah Novelli, Francesca Motta, Marianna Cerrato, Davide Olivari, Annasimon Salama, Francesca Fumagalli, Roberto Latini, Lidia Staszewsky, Luca Crippa,et al.
MDPI AG
Duchenne muscular dystrophy (DMD) is the most common form of muscle degenerative hereditary disease. Muscular replacement by fibrosis and calcification are the principal causes of progressive and severe musculoskeletal, respiratory, and cardiac dysfunction. To date, the D2.B10-Dmdmdx/J (D2-mdx) model is proposed as the closest to DMD, but the results are controversial. In this study, the cardiac structure and function was characterized in D2-mdx mice from 16–17 up to 24–25 weeks of age. Echocardiographic assessment in conscious mice, gross pathology, and histological and cardiac biomarker analyses were performed. At 16–17 weeks of age, D2-mdx mice presented mild left ventricular function impairment and increased pulmonary vascular resistance. Cardiac fibrosis was more extended in the right ventricle, principally on the epicardium. In 24–25-week-old D2-mdx mice, functional and structural alterations increased but with large individual variation. High-sensitivity cardiac Troponin T, but not N-terminal pro-atrial natriuretic peptide, plasma levels were increased. In conclusion, left ventricle remodeling was mild to moderate in both young and adult mice. We confirmed that right ventricle epicardial fibrosis is the most outstanding finding in D2-mdx mice. Further long-term studies are needed to evaluate whether this mouse model can also be considered a model of DMD cardiomyopathy.

Brain kynurenine pathway and functional outcome of rats resuscitated from cardiac arrest
Jacopo Lucchetti, Francesca Fumagalli, Davide Olivari, Roberta Affatato, Claudia Fracasso, Daria De Giorgio, Carlo Perego, Francesca Motta, Alice Passoni, Lidia Staszewsky,et al.
Ovid Technologies (Wolters Kluwer Health)
Background Brain injury and neurological deficit are consequences of cardiac arrest (CA), leading to high morbidity and mortality. Peripheral activation of the kynurenine pathway (KP), the main catabolic route of tryptophan metabolized at first into kynurenine, predicts poor neurological outcome in patients resuscitated after out‐of‐hospital CA. Here, we investigated KP activation in hippocampus and plasma of rats resuscitated from CA, evaluating the effect of KP modulation in preventing CA‐induced neurological deficit. Methods and Results Early KP activation was first demonstrated in 28 rats subjected to electrically induced CA followed by cardiopulmonary resuscitation. Hippocampal levels of the neuroactive metabolites kynurenine, 3‐hydroxy‐anthranilic acid, and kynurenic acid were higher 2 hours after CA, as in plasma. Further, 36 rats were randomized to receive the inhibitor of the first step of KP, 1‐methyl‐DL‐tryptophan, or vehicle, before CA. No differences were observed in hemodynamics and myocardial function. The CA‐induced KP activation, sustained up to 96 hours in hippocampus (and plasma) of vehicle‐treated rats, was counteracted by the inhibitor as indicated by lower hippocampal (and plasmatic) kynurenine/tryptophan ratio and kynurenine levels. 1‐Methyl‐DL‐tryptophan reduced the CA‐induced neurological deficits, with a significant correlation between the neurological score and the individual kynurenine levels, as well as the kynurenine/tryptophan ratio, in plasma and hippocampus. Conclusions These data demonstrate the CA‐induced lasting activation of the first step of the KP in hippocampus, showing that this activation was involved in the evolving neurological deficit. The degree of peripheral activation of KP may predict neurological function after CA.

Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial
Laura Alagna, Jennifer M. T. A. Meessen, Giacomo Bellani, Daniela Albiero, Pietro Caironi, Irene Principale, Luigi Vivona, Giacomo Grasselli, Francesca Motta, Nicolò M. Agnelli,et al.
Springer Science and Business Media LLC
Abstract Background The role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits. We aimed to elucidate the possible association and clinical significance between circulating levels of immunoglobulins. Methods In a subset of 956 patients with severe sepsis and septic shock of the multicentre, open-label RCT ALBIOS, venous blood samples were serially collected 1, 2, and 7 days after enrolment (or at ICU discharge, whichever came first). IgA, IgG and IgM concentrations were assayed in all patients on day 1 and in a subgroup of 150 patients on days 2 and 7. Ig concentrations were measured employing a turbidimetric assay, OSR61171 system. Results IgA on day 1 had a significant predictive value for both 28-day and 90-day mortality (28-day mortality, HR: 1.50 (95% CI 1.18–1.92); 90-day mortality, HR: 1.54 (95% CI 1.25–1.91)). IgG, but not IgM, on day 1 showed similar results for 28-day (HR 1.83 (95% CI 1.33–2.51) and 90-day mortality HR: 1.66 (95% CI 1.23–2.25)). In addition, lower levels of IgG but not of IgA and IgM, at day 1 were associated with significantly higher risk of secondary infections (533 [406–772] vs 600 [452–842] mg/dL, median [Q1–Q3], p = 0.007). Conclusions In the largest cohort study of patients with severe sepsis or septic shock, we found that high levels of IgA and IgG on the first day of diagnosis were associated with a decreased 90-day survival. No association was found between IgM levels and survival. As such, the assessment of endogenous immunoglobulins could be a useful tool to identify septic patients at high risk of mortality. Trial registration #NCT00707122, Clinicaltrial.gov, registered 30 June 2008