Pathophysiological role of inflammatory molecules in paediatric ischaemic brain injury

Abstract

Ischaemic stroke is one of the major causes of death and lifelong disability also in the paediatric population. Strong scientific effort has been put to clarify the pathophysiology of this disease in adults. However, only few studies have been performed in children. Preliminary results indicate that pathophysiological processes might differently affect the poststroke neuronal injury in neonates as compared to children. During the neural development, selective molecular mechanisms might be differently triggered by an ischaemic insult, thus potentially resulting in defined postischaemic clinical outcomes. Basic research studies in neonatal animal models of cerebral ischaemia have recently shown a potential role of soluble inflammatory molecules (such as cytokines, chemokines and oxidants) as pivotal players of neuronal injury in both perinatal and childhood ischaemic stroke. Although larger clinical trials are still needed to confirm these preliminary results, the potential benefits of selective treatments targeting inflammation in perinatal asphyxia encephalopathy might represent a promising investigation field in the near future. In this review, we will update evidence on the pathophysiological role of soluble inflammatory mediators in neonatal and childhood ischaemic stroke. Recent evidence on potential anti-inflammatory treatments to improve paediatric stroke prognosis will be discussed.

Cerebral ischemia initiates an immediate innate immune response in neonates during cardiac surgery

“…Data on the immune response to cerebral ischemia in neonates is scarce. There have been studies on the effects of perinatal asphyxia, which show a burst in cytokines and activation of neutrophils and monocytes within 24 hours, similar to the response in adults [10-15]. …”

The Ischemic Immature Brain: Views on Current Experimental Models

“…Confirmation by imaging or neuropathological studies is always mandatory (Govaert et al, 2009). Different risk factors have been recognized for perinatal stroke (Supplementary Table 1; Kurnik et al, 2003; Mirabelli-Badenier et al, 2012; Kasdorf and Perlman, 2013; Basu, 2014; Fernández-López et al, 2014; Kratzer et al, 2014; Machado et al, 2015; Buerki et al, 2016) but inflammation seems to be a prevalent underlying mechanism (Vexler and Yenari, 2009; Hagberg et al, 2015). For instance, chorioamnionitis, a bacterial infection of the amniochorionic membranes (Kasdorf and Perlman, 2013; Buerki et al, 2016) often leads to a longer labor period and worse prognosis (Vexler and Yenari, 2009).…”

“…Given the complex pathophysiology and difficulty in obtaining an early and accurate diagnosis, new therapies are being tested, alone or in combination with hypothermia, to improve global outcome. Some include administration of growth factors, anticoagulant and antiplatelet agents, blood uric acid lowering medication, antioxidant and anti-inflammatory molecules, stem cells-based therapy and electrical stimulation (Cnossen et al, 2009; Gonzalez and Ferriero, 2009; Mirabelli-Badenier et al, 2012; Basu, 2014; Fernández-López et al, 2014; Kratzer et al, 2014). …”

Endothelial Nitric Oxide Synthase and Neurodevelopmental Disorders

“…Cerebral ischemia induces an inlammatory response in the brain parenchyma and systemic circulation [34,35], resulting in the augmented secretion of proinlammatory cytokines and chemotactic molecules by the vascular endothelium in newborn infants with hypoxic-ischemic injury. Hence, cytokines are important upstream efector of brain injury after ischemia [36].…”