In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

Abstract

The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1 H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O 2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 Al centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios ( P b 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia. D 2005 Elsevier B.V. All rights reserved.Theme: Other systems of the CNS Topic: Brain metabolism and blood flow

Perinatal Iron Deficiency Predisposes the Developing Rat Hippocampus to Greater Injury from Mild to Moderate Hypoxia—Ischemia

“…Similar neurochemical changes have been showed in the hippocampus exposed to chronic hypoxia that was also iron-deficient (Raman et al, 2005). Taken together, these neurochemical changes suggest that hypoxia without ischemia may alter neuronal and glial integrities and energy metabolism in an irondeficient hippocampus.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…Recurrent exposure to hypoxia periods during development leads to the establishment of chronic neurochemical alterations of a different nature, particularly aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myo-inositol, NAA, phosphorylethanolamine (Raman et al, 2005;Rao et al, 2006). The increased PCr/Cr and Glu/Gln ratios and GABA levels are consistent with decreased brain energy consumption and impaired neurotransmission.…”

Cerebral Glutamine and Glutamate Levels in Relation to Compromised Energy Metabolism: A Microdialysis Study in Subarachnoid Hemorrhage Patients

“…Decreased interstitial Gln/Glt ratios have been reported in acute and chronic brain injuries such as traumatic brain injury (Cavus et al, 2005;Richards et al, 2003), hypoxia (Raman et al, 2005), and epilepsy (Labiner et al, 1999;Petroff et al, 2002;Samuelsson et al, 2003). Impaired Glt-Gln cycling because of compromised energy metabolism was the proposed mechanism behind the high interstitial Glt levels and the low interstitial Gln levels in those studies.…”