Potential protective role of endogenous glutamate‐oxaloacetate transaminase against glutamate excitotoxicity in fetal hypoxic–ischaemic asphyxia

Abstract

GOTGlutamate-oxaloacetate transaminase AIM Fetal blood contains higher concentrations of glutamate-oxaloacetate transaminase (GOT; a blood enzyme able to metabolize glutamate) than maternal blood. The aim of this study was to determine the relationship between GOT and glutamate levels in arterial blood samples from umbilical cord in control newborn infants and newborn infants with hypoxicischaemic insult and/or symptoms of hypoxia-ischemia after delivery.METHOD A total of 46 newborn infants (28 females, 18 males) were prospectively included in the study. Twenty-three infants (18 females, five males) were included as control participants and 23 (10 females, 13 males) were included as newborn infants at risk of adverse neurological outcome (defined as umbilical blood with pH <7.1). RESULTS Analysis of glutamate concentration and GOT activity in umbilical blood samplesshowed that newborn infants with pH <7.

Hepatic damage and glutamate oxaloacetate transaminase elevations during fetal asphyxia

“…In order to strengthen this theory, we analyzed the levels of GPT and GGT as the most specific markers of hepatic damage, and creatine kinase (CK) as a marker of muscle or cardiac damage, in the same serum samples from newborn infants previously included in the GOT study. 2 In line with our previous study, 2 GOT activity from umbilical blood samples was significantly higher in newborn infants with fetal asphyxia than in the control group; however, analysis of GPT activity levels showed no significant differences between the two groups ( Fig. 1 and Table SI, online supplementary information).…”

“…Due to the capacity of GOT to metabolize glutamate, it was suggested that during fetal development this enzyme could act as an endogenous protective mechanism involved in the control of glutamate homeostasis. 2 However, in addition to acute encephalopathy, severe birth asphyxia may induce variable damage in other peripheral organs, such as the hepatic system, which could lead the transient increase of GOT and other serum enzymes, such as glutamate pyruvate transaminase (GPT) or gamma glutamyl transferase (GGT). 3 Therefore, it can tentatively be postulated that the increase in GOT previously described in HIE 2 could be the result of the effect of asphyxia on systemic organs, and not due to endogenous protective mechanisms acting against glutamate excitotoxicity.…”

Perinatal compromise contributes to programming of GABAergic and glutamatergic systems leading to long‐term effects on offspring behaviour

“…Glutamate is required for appropriate neurodevelopment; however, elevated glutamate levels can have devastating effects. Excessive release of glutamate can occur following foetal hypoxia and ischaemia as a result of placental insufficiency and as a consequence of preterm birth . Excess glutamate leads to heightened excitation and excitotoxicity, which are major contributors to brain injury in compromised pregnancies .…”

Evidence for a mechanism to lower glutamate levels in fetal hypoxia–ischemia caused by asphyxia

“…3 The paper by P erez-Mato et al describes evidence for a novel mechanism of neuroprotection that might reduce the level of glutamate in the developing brain by enhancing its metabolism to the non-toxic metabolite a-ketoglutarate by the ubiquitous enzyme glutamate-oxaloacetate transaminase (GOT). 4 They measured levels of glutamate and GOT in serum from the umbilical cord of term infants with and without evidence of hypoxic-ischemic encephalopathy and found that both were elevated in those with hypoxicischemic encephalopathy. Regression analysis showed highly significant correlations between higher serum glutamate levels, and lower blood pH and APGAR scores at birth, as well as a highly significant correlation between serum GOT and serum glutamate levels.…”

“…Up to 20% of childhood arterial ischaemic stroke (AIS) is due to cervicocephalic arterial dissection (CCAD). [1][2][3] Establishing the presence of dissection is critical, as CCAD is associated with a significant risk of recurrent stroke, 4 which can be decreased with antithrombotic therapy. Diagnosis of vertebral artery dissection (VAD) is particularly challenging in childhood, as head and neck pain is not prominent, 1 and symptoms of posterior circulation stroke such as vomiting and dizziness are common and nonspecific childhood complaints.…”