title: Brain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease.
abstract: To characterize the cerebral profile associated with sickle cell disease (SCD), we used in vivo proton MRI and MRS to quantify hemodynamics and neurochemicals in the thalamus of NY1DD mice, a mild model of SCD, and compared them with wild-type (WT) control mice. Compared with WT mice, NY1DD mice at steady state had elevated cerebral blood flow (CBF) and concentrations of N-acetylaspartate (NAA), glutamate (Glu), alanine, total creatine and N-acetylaspartylglutamate. Concentrations of glutathione (GSH) at steady state showed a negative correlation with BOLD signal change in response to 100% oxygen, a marker for oxidative stress, and mean diffusivity assessed using diffusion-tensor imaging, a marker for edematous inflammation. In NY1DD mice, elevated basal CBF was correlated negatively with [NAA], but positively with concentration of glutamine ([Gln]). Immediately after experimental hypoxia (at reoxygenation after 18 hours of 8% O2), concentrations of NAA, Glu, GSH, Gln and taurine (Tau) increased only in NY1DD mice. [NAA], [Glu], [GSH] and [Tau] all returned to baseline levels two weeks after the hypoxic episode. The altered neurochemical profile in the NY1DD mouse model of SCD at steady state and following experimental hypoxia/reoxygenation suggests a state of chronic oxidative stress leading to compensatory cerebral metabolic adjustments.
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Radiology, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Cui
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Suzuka
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Aerospace Engineering, Georgia Tech, Atlanta, GA, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Branch
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Kamalakar
authors.initials: K
authors.lastname: Ambadipudi
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Thangaswamy
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Medicine (Hematology), Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Seetharama A
authors.initials: SA
authors.lastname: Acharya
authors.affiliation: Department of Medicine (Hematology), Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Henny H
authors.initials: HH
authors.lastname: Billett
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Radiology, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Branch
mesh_terms: D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001704:Biopolymers / Q000378:metabolism*; D001783:Blood Flow Velocity; D001921:Brain / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057054:Molecular Imaging; D010101:Oxygen Consumption; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D015415:Biomarkers; D001704:Biopolymers
keywords: NAA; cerebral blood flow; glutamate; glutathione; hypoxia; mice; oxidative stress; sickle cell disease