The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury.
The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-(13)C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using (1)H- and (13)C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Eva M F
EM
Brekke
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Tora S
TS
Morken
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Marius
M
Widerøe
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Asta K
AK
Håberg
1] Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway [2] Department of Pediatrics, St Olav University Hospital, Central Norway Regional Health Authority, Trondheim, Norway.
Ann-Mari
AM
Brubakk
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Ursula
U
Sonnewald
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D019906:Nuclear Magnetic Resonance, Biomolecular; D010427:Pentose Phosphate Pathway / Q000502:physiology*; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D051381:Rats
D011766:Pyruvate Carboxylase; D005947:Glucose