Dichloroacetate treatment improves mitochondrial metabolism and reduces brain injury in neonatal mice

• The purpose of this study was to evaluate the effect of dichloroacetate (DCA) treatment for brain injury in neonatal mice after hypoxia ischemia (HI) and the possible molecular mechanisms behind this effect. Postnatal day 9 male mouse pups were subjected to unilateral HI, DCA was injected intraperitoneally immediately after HI, and an additional two doses were administered at 24 h intervals. The pups were sacrificed 72 h after HI. Brain injury, as indicated by infarction volume, was reduced by 54.2% from 10.8 +/- 1.9 mm(3) in the vehicle-only control group to 5.0 +/- 1.0 mm(3) in the DCA-treated group at 72 h after HI (p = 0.008). DCA treatment also significantly reduced subcortical white matter injury as indicated by myelin basic protein staining (p = 0.018). Apoptotic cell death in the cortex, as indicated by counting the cells that were positive for apoptosis-inducing factor (p = 0.018) and active caspase-3 (p = 0.021), was significantly reduced after DCA treatment. The pyruvate dehydrogenase activity and the amount of acetyl-CoA in mitochondria was significantly higher after DCA treatment and HI (p = 0.039, p = 0.024). In conclusion, DCA treatment reduced neonatal mouse brain injury after HI, and this appears to be related to the elevated activation of pyruvate dehydrogenase and subsequent increase in mitochondrial metabolism as well as reduced apoptotic cell death.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

apoptosis

autophagy

brain ischemia

mitochondria

pyruvate dehydrogenase

Pathology Section

hypoxic-ischemic encephalopathy

congenital lactic-acidosis

caloric

restriction mimetics

controlled clinical-trial

in-vivo

energy

metabolites

cerebral-ischemia

cell-death

autophagy

neuroprotection

ang lh

1992

journal of cerebral blood flow and metabolism

v12

p1030

Publikations- och innehållstyp

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