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Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment.


ABSTRACT: Ru360, a mitochondrial Ca2+ uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 and 72 h, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD+ depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas.

SUBMITTER: Chitturi J 

PROVIDER: S-EPMC7904607 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment.

Chitturi Jyothsna J   Santhakumar Vijayalakshmi V   Kannurpatti Sridhar S SS  

Mitochondrion 20210121


Ru360, a mitochondrial Ca<sup>2+</sup> uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 and 72 h, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD<sup>+</sup> depl  ...[more]

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