Marcadores anatómicos y bioquímicos de pronóstico neurológico en un modelo murino de hemorragia intracerebroventricular en el recién nacido pretérmino

Resumen

Germinal matrix-intraventricular haemorrhage remains a serious problem in the preterm newborn and the significant increase of survival rates in extreme preterm infants has also contributed to increase the absolute number of patients developing GMH-IVH. However animal models to further understand the underlying mechanisms and available peripheral markers or prognostic tools are limited. In order to further characterize central complications and evolution of germinal matrix-intraventricular hemorrhage we have injected collagenase intraventricularly to P7 CD1 mice and we have assessed them in the short (P14) and the long term (P70). Early complications included ventricle enlargement, increased bleeding and inflammation. All these alterations were maintained in the long term, and increased tau phosphorylation and neurogenesis compromise were also observed, resulting all together in impaired learning and memory in the early adulthood (P70). We have also analyzed feasible peripheral markers, both in this animal model and in preterm newborns with germinal matrix-intraventricular hemorrhage. While MMP9 levels were not significantly affected in mice or infants, reduced gelsolin levels and increased ubiquitin carboxy-terminal hydrolase L1 and tau levels were detected at birth time in germinal matrix-intraventricular hemorrhage patients, and a similar pattern was observed in our animal model after hemorrhage. Interestingly, early changes in gelsolin and carboxy-terminal hydrolase L1 levels were significantly correlated with the hemorrhage grade in children. Altogether, our data support the utility of this animal model to reproduce central complications and peripheral changes observed in the clinic and opens the door to consider gelsolin, carboxy-terminal hydrolase L1 and tau as feasible predictors to develop germinal matrix-intraventricular hemorrhage.