title: Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury.
abstract: Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000mg/kg, i.p.) or ethyl pyruvate (EP; 40mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40mg/kg of EP being as effective as 1000mg/kg of SP, and multiple treatments within 6h of injury did not improve upon outcomes seen following a single treatment.
authors.affiliation: UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA. Electronic address: moro.nobuhiro@nihon-u.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Moro
authors.affiliation: UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA. Electronic address: sghavim@mednet.ucla.edu.
authors.forename: Sima S
authors.initials: SS
authors.lastname: Ghavim
authors.affiliation: UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA. Electronic address: ngharris@mednet.ucla.edu.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Harris
authors.affiliation: UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA. Electronic address: dhovda@mednet.ucla.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
authors.affiliation: UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6901, USA. Electronic address: rsutton@ucla.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sutton
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019289:Pyruvic Acid / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019289:Pyruvic Acid; D005947:Glucose
keywords: (14)C-2DG; Controlled cortical impact; Fluoro-Jade B; Pyruvate; Rat