Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1-13 C]pyruvate.
Magn Reson Med
; 90(6): 2432-2442, 2023 12.
Article
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| MEDLINE
| ID: mdl-37427535
ABSTRACT
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 T2 -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.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Lesiones Encefálicas
/
Lesiones Traumáticas del Encéfalo
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Magn Reson Med
Asunto de la revista:
DIAGNOSTICO POR IMAGEM
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos