AUTHOR=Eisenhut Michael , Choudhury Samyami 

TITLE=In Premature Newborns Intraventricular Hemorrhage Causes Cerebral Vasospasm and Associated Neurodisability via Heme-Induced Inflammasome-Mediated Interleukin-1 Production and Nitric Oxide Depletion

JOURNAL=Frontiers in Neurology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00423

DOI=10.3389/fneur.2017.00423

ISSN=1664-2295

ABSTRACT=Background: Intraventricular haemorrhage (IVH) occurs in 60-70% of neonates weighing 500-750 g and 10-20% of those weighing 1,000-1,500 g. All forms of IVH have been associated with neurocognitive deficits. Both subarachnoid and intraventricular haemorrhages have been associated with delayed vasospasm leading to neurological deficits. Pathways linking haemoglobin release from blood clots to vasospasm include heme induced activation of inflammasomes releasing interleukin-1 (IL-1) which can cause calcium dependent and independent vasospasm. Free haemoglobin is a potent scavenger of nitric oxide. Depletion of nitric oxide, a potent endogenous vasodilator, has been associated with features of vasospasm. 
Hypothesis: In premature newborns intraventricular haemorrhage causes cerebral vasospasm and associated neurodisability via heme induced increased inflammasome mediated interleukin-1 production and nitric oxide depletion.
Confirmation of hypothesis and implications: This hypothesis could be confirmed in the intraventricular haemorrhage animal model with visualisation of any associated vasospasm by angiography and in newborns with IVH by transcranial doppler ultrasonography and correlation with cerebrospinal fluid interleukin-1 and nitric oxide metabolite levels. Confirmation of the role of heme in activation of inflammasomes causing IL-1 production and nitric oxide binding could be achieved by measuring the effect of heme scavenging interventions on IL-1 levels and levels of nitric oxide metabolites. In addition to removal of the accumulated blood of an IVH by drainage, irrigation and fibrinolytic therapy intrathecal application of vasodilators and heme scavenging agents like haptoglobin and haemopexin and systemic treatment with inhibitors of inflammasomes like ruscogenin or telmisartan could be used to prevent and treat cerebral vasospasm and thus reduce the risk of associated brain injury in premature neonates.