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Localized proton MRS of cerebral metabolite profiles in different mouse strains
Attila Schwarcz1, Oliver Natt, Takashi Watanabe
1Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Abstract:
Localized proton MR spectroscopy (MRS) was used to quantify cerebral metabolite concentrations in NMRI (n = 8), BALB/c (n = 7), and C57BL/6 (n = 8) mice in vivo and 1 hr after global irreversible ischemia (2.35 T, STEAM, TR/TE/TM = 6000/20/10 ms, 4 x 3 x 4 mm(3) volume, corrections for cerebrospinal fluid). Anatomical MRI and proton MRS revealed significant differences of the C57BL/6 strain in comparison with both BALB/c and NMRI mice. While MRI volumetry yielded larger ventricular spaces of the C57BL/6 strain, proton MRS resulted in elevated concentrations of N-acetylaspartate (tNAA), creatine and phosphocreatine (tCr), choline-containing compounds (Cho), glucose (Glc), and lactate (Lac) relative to BALB/c mice and elevated Glc relative to NMRI mice. Apart from the expected decrease of Glc and increase of Lac 1 hr post mortem, C57BL/6 mice presented with significant reductions of tNAA, tCr, and Cho, whereas these metabolites remained unchanged in BALB/c and NMRI mice. The results support the hypothesis that the more pronounced vulnerability of C57BL/6 mice to brain ischemia is linked to strain-dependent differences of the cerebral energy metabolism.
Insights
C57BL/6 mice exhibit distinct cerebral metabolite profiles and greater vulnerability to brain ischemia compared to BALB/c and NMRI strains. These strain-dependent differences in cerebral energy metabolism influence ischemic outcomes.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Cerebral metabolite concentrations vary between mouse strains.
- Understanding strain-specific responses to ischemia is crucial for preclinical research.
Purpose of the Study:
- To quantify cerebral metabolite concentrations in different mouse strains (NMRI, BALB/c, C57BL/6) using proton Magnetic Resonance Spectroscopy (MRS).
- To investigate strain-dependent differences in brain metabolism and vulnerability to global irreversible ischemia.
Main Methods:
- Localized proton MRS (2.35 T, STEAM sequence) was performed in vivo and post-mortem on three mouse strains.
- Anatomical MRI was used for volumetry, with corrections for cerebrospinal fluid.
- Metabolite concentrations (N-acetylaspartate, creatine, phosphocreatine, choline, glucose, lactate) were quantified.
Main Results:
- C57BL/6 mice showed larger ventricular spaces compared to BALB/c and NMRI mice.
- Proton MRS revealed elevated N-acetylaspartate, creatine, phosphocreatine, choline, glucose, and lactate in C57BL/6 mice relative to BALB/c.
- Post-ischemia, C57BL/6 mice exhibited significant reductions in N-acetylaspartate, creatine, and choline, unlike BALB/c and NMRI mice.
Conclusions:
- Significant strain-dependent differences exist in cerebral metabolite concentrations and energy metabolism among NMRI, BALB/c, and C57BL/6 mice.
- The observed metabolic profile in C57BL/6 mice is associated with their increased vulnerability to global brain ischemia.