Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1- 13 C]pyruvate.

Autor: Hackett EP; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., Chen J; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., Ingle L; Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., Al Nemri S; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., Barshikar S; Department of Physical Medicine and Rehabilitation, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., da Cunha Pinho M; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., Plautz EJ; Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, Texas, USA., Bartnik-Olson BL; Department of Radiology, Loma Linda University, Loma Linda, California, USA., Park JM; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.; Department of Biomedical Engineering, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Jazyk: angličtina
Zdroj: Magnetic resonance in medicine [Magn Reson Med] 2023 Dec; Vol. 90 (6), pp. 2432-2442. Date of Electronic Publication: 2023 Jul 10.
DOI: 10.1002/mrm.29794
Abstrakt: Purpose: [ 13 C]Bicarbonate formation from hyperpolarized [1- 13 C]pyruvate via pyruvate dehydrogenase, a key regulatory enzyme, represents the cerebral oxidation of pyruvate and the integrity of mitochondrial function. The present study is to characterize the chronology of cerebral mitochondrial metabolism during secondary injury associated with acute traumatic brain injury (TBI) by longitudinally monitoring [ 13 C]bicarbonate production from hyperpolarized [1- 13 C]pyruvate in rodents.
Methods: Male Wistar rats were randomly assigned to undergo a controlled-cortical impact (CCI, n = 31) or sham surgery (n = 22). Seventeen of the CCI and 9 of the sham rats longitudinally underwent a 1 H/ 13 C-integrated MR protocol that includes a bolus injection of hyperpolarized [1- 13 C]pyruvate at 0 (2 h), 1, 2, 5, and 10 days post-surgery. Separate CCI and sham rats were used for histological validation and enzyme assays.
Results: In addition to elevated lactate, we observed significantly reduced bicarbonate production in the injured site. Unlike the immediate appearance of hyperintensity on T 2 -weighted MRI, the contrast of bicarbonate signals between the injured region and the contralateral brain peaked at 24 h post-injury, then fully recovered to the normal level at day 10. A subset of TBI rats demonstrated markedly increased bicarbonate in normal-appearing contralateral brain regions post-injury.
Conclusion: This study demonstrates that aberrant mitochondrial metabolism occurring in acute TBI can be monitored by detecting [ 13 C]bicarbonate production from hyperpolarized [1- 13 C]pyruvate, suggesting that [ 13 C]bicarbonate is a sensitive in-vivo biomarker of the secondary injury processes.
(© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)
Databáze: MEDLINE
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