Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain

Abstract

Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo ¹H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P < 0.01) and [glutamate]/[glutamine] ratio (P < 0.05). Lower taurine concentrations were observed in the hippocampus (P < 0.01) and striatum (P < 0.05). IUGR differentially affects the neurochemical profile of the P7 rat brain regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

Keywords: Brain; IUGR; Magnetic resonance spectroscopy; Metabolism.

Figure 1. Representative spectra from the postnatal day 7 rat cerebral cortex, hippocampus and striatum of normally grown (NG) control and IUGR brains

All spectra were acquired from VOI using a LASER localization sequence (repetition time TR = 5s, echo time TE = 15ms, NT=128, VOI = 6–18μl) combined with VAPOR water suppression. Abbreviations: macromolecules (Mac), ascorbate (Asc), aspartate (Asp), creatine (Cr), phosphocreatine (PCr), γ-aminobutyric acid (GABA), glucose (Glc), glutamate (Glu), glutamine (Gln), glutathione (GSH), lactate (Lac), myo-inositol (Ins), N–acetylaspartate (NAA), N-acetylaspartyglutamate (NAAG), phosphoethanolamine (PE), taurine (Tau), the sum of glycerophosphocholine and phosphocholine (GPC+PC).

Figure 2. Neurochemical profile of the cerebral cortex, hippocampus and striatum in the P7 NG and IUGR rat brains

NG is represented by the black bars, IUGR by the white bars. IUGR affected more neurochemicals in the cortex than in the hippocampus or striatum. *P<0.01, #P<0.05. All data are represented as mean±SD. All metabolite concentrations are expressed in μmol/g. Macromolecule content is expressed in a.i. and the [Glu]/[Gln] ratio is dimensionless. Cortex (NG n=13, IUGR n=10), hippocampus (NG n=8, IUGR n=12) and striatum (NG n=13, IUGR n=9). Abbreviations: macromolecules (Mac), ascorbate (Asc), aspartate (Asp), creatine (Cr), phosphocreatine (PCr), γ-aminobutyric acid (GABA), glucose (Glc), glutamate (Glu), glutamine (Gln), glutathione (GSH), lactate (Lac), myo-inositol (Ins), N-acetylaspartate (NAA), N-acetylaspartyglutamate (NAAG), phosphoethanolamine (PE), taurine (Tau), the sum of glycerophosphocholine and phosphocholine (GPC+PC), total creatine (PCr+Cr), glutamate/glutamine ratio ([Glu]/[Gln]).