Circulating Biochemical Markers of Brain Damage in Infants Complicated by Ischemia Reperfusion Injury

Abstract

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents of calcium mediated effects could be responsible for reperfusion injury, which, in turns, leads to cerebral hemorrhage and damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia or cardiovascular disorders treated by risky procedures such as open heart surgery and cardiopulmonary by-pass (CPB). To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein; neuronal specific enolase (NSE), a dimeric isoenzyme; glial fibrillary acid protein (GFAP), a astroglial protein, in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia or cardiovascular disorders requiring risky therapeutic strategies such as CPB and/or extracorporeal membrane oxygenation.

Motor Deficits Are Triggered by Reperfusion-Reoxygenation Injury as Diagnosed by MRI and by a Mechanism Involving Oxidants

“…This has also been postulated in perinatal stroke (Gazzolo et al, 2009). However, most cases of perinatal injury involve global hypoxia and ischemia (H-I) and reperfusion rather than the focal injury of stroke.…”

“…Reperfusion injury in fetal brain has never been shown directly in cases of acute placental insufficiency such as abruptio placenta, possibly due to a lack of suitable biomarkers. Since antepartum hypoxia-ischemia (H-I) is a major cause of cerebral palsy (CP) (Gazzolo et al, 2009), we developed a model of CP involving global H-I and reperfusion-reoxygenation (Tan et al, 2005). …”

Pretreatment with 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside Attenuates Cerebral Ischemia/Reperfusion-Induced Injury In Vitro and In Vivo

“…The rapid initiation of reperfusion therapy is an effective strategy to reduce the infarct area and minimize the behavioral deficits resulting from ischemia. However, reperfusion itself is associated with injury as a result of the overproduction of reactive oxygen species and overloading of calcium that occur in the early reperfusion period [5], [6], [7]. The oxygen-glucose deprivation followed by reperfusion (OGD-R) model mimics the key pathophysiological events of ischemia in vitro and enables the dissection of cellular events without affecting oxygen and metabolites [8].…”

Protein S100β in Late-Pregnancy Fetuses with Low Birth Weight and Abnormal Cerebroplacental Ratio

“…Recent research has evaluated the anatomical and functional substrates in this pathology, showing the existence of structural anomalies in fetal brain fissures and cerebral connections as well as functional anomalies that suggest suboptimal neural networking and cortical maturation [17][18][19] . FGR may also lead to direct neuronal damage increasing the leakage of specific markers, especially during early-onset FGR and acute-labor hypoxia [20][21][22] , but there is less evidence of this mechanism in late-onset FGR, possibly because the hypoxia is milder or of a shorter duration prior to birth.…”