1H-NMR Spectroscopy of Cerebrospinal Fluid of Fetal Sheep during Hypoxia-Induced Acidemia and Recovery

Abstract

The purpose of the study was to investigate the sequence of processes occurring during and after hypoxia-induced acidemia. We used proton nuclear magnetic resonance spectroscopy, which provides an overview of metabolites in cerebrospinal fluid (CSF), reflecting neuronal metabolism and damage. The pathophysiological condition of acute fetal asphyxia was mimicked by reducing maternal uterine blood flow in 14 unanesthetized pregnant ewes. CSF metabolites were measured during hypoxia-induced acidemia, and during the following recovery period, including the periods at 24 and 48 h after the hypoxic insult. Maximum values of the following CSF metabolites were reached during severe hypoxia (pH <or= 7.00): glucose, lactate, pyruvate, hypoxanthine, alanine, beta-hydroxybutyrate, choline, creatine, myo-inositol, citrate, succinate, valine, and an unknown metabolite characterized by a resonance at 1.56 ppm in the proton nuclear magnetic resonance spectrum. Twenty-four hours after the hypoxic insult, myo-inositol was increased, and alanine was decreased 48 h after the hypoxic insult, both compared with control values. Choline levels in CSF had a linear relationship with arterial pH (r = 0.26, p < 0.005). During severe hypoxia, CSF levels of succinate and choline are increased. Increased CSF levels of succinate may indicate dysfunction of the mitochondrial respiratory chain, whereas elevated CSF choline levels may indicate disrupted cell membranes. The increase of the CSF myo-inositol level after 24 and 48 h may indicate osmolytic cell changes causing cell edema. Decreased alanine level may represent changes in the source of excitatory amino acid synthesis.

Urine metabolomic profiling of children with respiratory tract infections in the emergency department: a pilot study

“…Further, when lactate is produced, alanine levels are expected to change as well as part of gluconeogensesis [19]. Alanine levels were increased in the urine of piglet models of hypoxia Skappak [20], in the CSF of fetal hypoxic sheep [21] and cellular cultures undergoing apoptosis [22]. Perturbations in acetoacetate can be identified during periods of physical exertion and training in otherwise healthy individuals [23].…”

Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

“…Succinate is a recognized marker of anaerobic metabolism in mammals. 31 Several metabolic pathways lead to succinate formation. Therefore, the mechanisms for succinate accumulation caused by propofol still require clarification in our model.…”

γ‐Hydroxybutyrate binds to the synaptic site recognizing succinate monocarboxylate: A new hypothesis on astrocyte–neuron interaction via the protonation of succinate

“…The expression of pyruvate carboxylase in astrocytes (but not neurons) enables astrocytes to synthesize SUC and CIT for release, which occurs at markedly different rates (SUC 1.5 nmol/hr/mg, CIT 70 nm/hr/mg; Westergaard et al, 1994a, b). Ranges of CIT and SUC concentrations in the fetal CSF seem to reflect these release rates, insofar as the CIT concentration falls within the range 74–327 μM, whereas SUC is not detectable (Van Cappellen Van Walsum et al, 2002). Appreciable binding of SUC can occur and can be measured by estimating the CSF level of SUC to fall within limits of its detection limit of 4–11 μM (Van Cappellen Van Walsum et al, 2002).…”

“…Lack of oxygen leads to impaired mitochondrial function and anaerobic metabolism, reflected by decreased extracellular CIT and increased lactate (LAC) levels (Ben‐Yoseph et al, 1993). This LAC‐based acidemia occurs under different pathophysiological conditions, such as ischemia and fetal hypoxia (Obrenovitch et al, 1990; Schneider et al, 1993; Van Cappellen Van Walsum et al, 2002). A final diagnosis of patients who had a cerebrospinal fluid (CSF) LAC concentration greater than 2 mM revealed seizures, inflammatory changes, and proved metabolic disorders (Chow et al, 2005).…”