Magnetic Resonance Spectroscopy Detects Neuroanatomically Specific Alterations in Brain Metabolites from Infancy to Adulthood in Birth Asphyxiated Rats
Magnetic resonance spectroscopy (MRS) provides a safe, non-invasive means of directly assessing biochemistry in localized brain regions of pediatric and adult populations. This technology holds much promise for early identification of developmental neural dysfunction, enabling early intervention. Herein, we report longitudinal, neuroanatomically specific metabolic profiles from neonatal life to adulthood in birth asphyxiated rats. Epidemiological evidence identifies obstetric complications, such as birth asphyxia, as risk factors in the emergence of psychiatric and cognitive dysfunction in later life. A single, moderate (12-15min) bout of experimentally controlled asphyxia in a rat fetus at term can exert persistent changes in brain morphology and behavior. On postnatal days (P) 7, 35 and 60, we acquired MRS metabolite profiles from male rats exposed to 12 min asphyxia (APX) at term and non-asphyxiated (NON) littermates. We hypothesized that APX rats would show signs of ongoing metabolic dysfunction at P7 (i.e. increased lactate) and in adulthood, decreased N-Acetylaspartate and N-acetylaspartylglutamate (NAA+NAAG) would indicate striatal damage and neuron loss. P7 profiles of a 27mm3 area (voxel) of subcortical tissue including striatum and surrounding tissue revealed a decrease in NAA+NAAG/total creatine (tCr) (t=2.061; p=0.0584) for APX compared to NON littermates (N=8). This difference did not persist at P35 or P60. However P60 APX rats showed reduced striatal taurine/tCr (t=2.34; p=0.035). In a second study underway (N=4), we increased asphyxia duration to 15 min and are conducting a longitudinal comparison of metabolites exclusively in dorsal striatum of APX and NON rats. Our preliminary findings show that on P7, but not P35 or P60, APX rats have significantly increased striatal lactate/tCr (t=2.51; p=0.046) and guanine/tCr (t=3.66; p=0.011), indicating delayed metabolic deficit following birth asphyxia. APX rats show increased striatal NAA+NAAG/tCr (t=2.33; p=0.058) on P35 and significantly reduced NAAG/tCr (t=-2.55; p=0.044) on P60, suggesting persistent striatal dysfunction in adulthood. These studies show different metabolite patterns based on precise voxel placement. In our second study, a smaller voxel (10-15mm3) solely incorporating dorsal striatum uncovered a broader pattern of changes, supporting our hypothesis of ongoing striatal metabolic disruption in neonates, with long term striatal damage in adulthood. This work highlights the need for specificity of voxel placement and identifies unique, tissue-specific pattern of metabolite changes throughout early life and into adulthood following birth asphyxia.
Morgan, J. J.,
Kleven, G. A.,
Feimster, J. D.,
Winn, G. G.,
Tulbert, C. D.,
& Ronca, A. E.
(2010). Magnetic Resonance Spectroscopy Detects Neuroanatomically Specific Alterations in Brain Metabolites from Infancy to Adulthood in Birth Asphyxiated Rats. Society for Neuroscience Abstracts.