Erythropoietin as a Neuroprotective Drug for Newborn Infants: Ten Years after the First Use

Protective strategies against perinatal brain injury represent a major challenge for modern neonatology. Erythropoietin (Epo) enhances endogenous mechanisms of repair and angiogenesis. In order to analyse the newest evidence on the role of Epo in prematurity, hypoxic ischemic encephalopathy (HIE) and perinatal stroke, a critical review using 2020 PRISMA statement guidelines was conducted. This review uncovered 26 clinical trials examining the use of Epo for prematurity and brain injury-related outcomes. The effects of Epo on prematurity were analysed in 16 clinical trials. Erythropoietin was provided until 32-35 weeks of corrected postnatal age with a dosage between 500-3000 UI/kg/dose. Eight trials reported the Epo effects on HIE term newborn infants: Erythropoietin was administered in the first weeks of life, at different multiple doses between 250-2500 UI/kg/dose, as either an adjuvant therapy with hypothermia or a substitute for hypothermia. Two trials investigated Epo effects in perinatal stroke. Erythropoietin was administered at a dose of 1000 IU/kg for three days. No beneficial effect in improving morbidity was observed after Epo administration in perinatal stroke. A positive effect on neurodevelopmental outcome seems to occur when Epo is used as an adjuvant therapy with hypothermia in the HIE newborns. Administration of Epo in preterm infants still presents inconsistencies with regard to neurodevelopmental outcome. Clinical trials show significant differences mainly in target population and intervention scheme. The identification of specific markers and their temporal expression at different time of recovery after hypoxia-ischemia in neonates might be implemented to optimize the therapeutic scheme after hypoxic-ischemic injury in the developing brain. Additional studies on tailored regimes, accounting for the risk stratification of brain damage in newborns, are required

Olfatto e autismo: studio clinico-sperimentale su bambini

Il disturbo dello spettro autistico (ASD) è definito come un disturbo del neurosviluppo, caratterizzato da difficoltà nell’interazione sociale, da deficit della comunicazione e dalla presenza di interessi ristetti e comportamenti ripetitivi, a cui si associa una peculiare percezione degli stimoli sensoriali. Questa tesi ha lo scopo di indagare la percezione olfattiva nei soggetti con diagnosi di disturbo dello spettro autistico. È stato condotto uno studio clinico-sperimentale su un campione di 20 bambini con diagnosi di autismo ad alto funzionamento e su un campione di controllo composto da 20 bambini con sviluppo neurologico tipico, appaiati per età, genere e livello cognitivo. Le due popolazioni sono state caratterizzate attraverso l’utilizzo di questionari. In entrambe è stato svolto un test per studiare la funzione olfattiva, indagando la capacità di identificare un odore, quella di discriminare due stimoli olfattivi diversi e la soglia di attivazione della percezione sensoriale in risposta ad un odore presentato a concentrazioni diverse. Questo studio ha permesso di individuare la presenza di una differenza statisticamente significativa per quanto riguarda il livello di soglia olfattiva e la capacità di identificazione, che risultano essere deficitarie nei soggetti con diagnosi di ASD rispetto ai soggetti con sviluppo neurologico tipico. Autistic Spectrum Disorder (ASD) is a neurodevelopmental disorder, characterized by difficulties in social interaction and communication and restricted interests and repetitive behaviours, also associated with a peculiar sensory processing. The aim of this study is to investigate olfaction in children with diagnosis of ASD. In our study, two different populations have been analysed: a sample of 20 children with diagnosis of high functioning autism and a sample of 20 normally developing children, matched by age, gender and cognitive level. Both populations have been characterised by the employment of questionnaires. In both of them, olfaction has been investigated, in order to define the ability to identify odors, to discriminate between two different olfactory stimuli and the sensory activation threshold in response to an olfactory stimulus. With this research, we found a statistically significant difference in olfactory threshold and ability to identify odors, which are deficient in individuals with ASD, compared to children with normal neurodevelopment

Olfactory Processing in Male Children with Autism: Atypical Odor Threshold and Identification

Sensory issues are of great interest in ASD diagnosis. However, their investigation is mainly based on external observation (parent reports), with methodological limitations. Unobtrusive olfactory assessment allows studying autism neurosensoriality. Here, 20 male children with high-functioning ASD and 20 matched controls were administered a complete olfactory test battery, assessing olfactory threshold, identification and discrimination. ASD children show lower sensitivity (p = 0.041), lower identification (p = 0.014), and intact odor discrimination (p = 0.199) than controls. Comparing olfactory and clinical scores, a significant correlation was found in ASD between olfactory threshold and the CBCL social problems (p = 0.011) and aggressive behavior (p = 0.012) sub-scales. The pattern featuring peripheral hyposensitivity, high-order difficulties in odor identification and regular subcortical odor discrimination is discussed in light of hypo-priors hypothesis for autism

MiR-133a regulates collagen 1A1: Potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension

MicroRNAs play an important role in myocardial diseases. MiR-133a regulates cardiac hypertrophy, while miR-29b is involved in cardiac fibrosis. The aim of this study was to evaluate whether miR-133a and miR-29b play a role in myocardial fibrosis caused by Angiotensin II (Ang II)-dependent hypertension. SpragueDawley rats were treated for 4 weeks with Ang II (200ng/kg/min) or Ang II+irbesartan (50mg/kg/day in drinking water), or saline by osmotic minipumps. At the end of the experimental period, cardiac miR-133a and miR-29b expression was measured by real-time PCR, and myocardial fibrosis was evaluated by morphometric analysis. A computer-based prediction algorithm led to the identification of collagen 1a1 (Col1A1) as a putative target of miR-133a. A reporter plasmid bearing the 3'-untranslated regions (UTRs) of Col1A1 mRNA was constructed and luciferase assay was performed. MiR-133a suppressed the activity of luciferase when the reporter gene was linked to a 3'-UTR segment of Col1A1 (P<0.01). Mutation of miR-133a binding sites in the 3'-UTR of Col1A1 mRNA abolished miR-133a-mediated repression of reporter gene activity, showing that Col1A1 is a real target of miR-133a. In vivo, Ang II caused an increase in systolic blood pressure (P<0.0001, tail cuff) and myocardial fibrosis in presence of a decrease in miR-133a (P<0.01) and miR-29b (P<0.01), and an increase in Col1A1 expression (P<0.01). These effects were abolished by Ang II administration+irbesartan. These data demonstrate a relationship between miR-133a and Col1A1, suggesting that myocardial fibrosis occurring in Ang II-dependent hypertension is regulated by the down-regulation of miR-133a and miR-29b through the modulation of Col1A1 expression. J. Cell. Physiol. 227: 850856, 2012. (C) 2011 Wiley Periodicals, Inc