title: Neuronal Cell Death Induced by Mechanical Percussion Trauma in Cultured Neurons is not Preceded by Alterations in Glucose, Lactate and Glutamine Metabolism.
abstract: Traumatic brain injury (TBI) is a devastating neurological disorder that usually presents in acute and chronic forms. Brain edema and associated increased intracranial pressure in the early phase following TBI are major consequences of acute trauma. On the other hand, neuronal injury, leading to neurobehavioral and cognitive impairments, that usually develop months to years after single or repetitive episodes of head trauma, are major consequences of chronic TBI. The molecular mechanisms responsible for TBI-induced injury, however, are unclear. Recent studies have suggested that early mitochondrial dysfunction and subsequent energy failure play a role in the pathogenesis of TBI. We therefore examined whether oxidative metabolism of (13)C-labeled glucose, lactate or glutamine is altered early following in vitro mechanical percussion-induced trauma (5 atm) to neurons (4-24 h), and whether such events contribute to the development of neuronal injury. Cell viability was assayed using the release of the cytoplasmic enzyme lactate dehydrogenase (LDH), together with fluorescence-based cell staining (calcein and ethidium homodimer-1 for live and dead cells, respectively). Trauma had no effect on the LDH release in neurons from 1 to 18 h. However, a significant increase in LDH release was detected at 24 h after trauma. Similar findings were identified when traumatized neurons were stained with fluorescent markers. Additionally (13)C-labeling of glutamate showed a small, but statistically significant decrease at 14 h after trauma. However, trauma had no effect on the cycling ratio of the TCA cycle at any time-period examined. These findings indicate that trauma does not cause a disturbance in oxidative metabolism of any of the substrates used for neurons. Accordingly, such metabolic disturbance does not appear to contribute to the neuronal death in the early stages following trauma.
authors.affiliation: Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Jayakumar
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: L K
authors.initials: LK
authors.lastname: Bak
authors.affiliation: Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL, USA.
authors.forename: K V
authors.initials: KV
authors.lastname: Rama Rao
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: H S
authors.initials: HS
authors.lastname: Waagepetersen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Schousboe
authors.affiliation: Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL, USA. mnorenbe@med.miami.edu.|Department of Pathology (D-33), University of Miami School of Medicine, P.O. Box 016960, Miami, FL, 33101, USA. mnorenbe@med.miami.edu.|Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL, USA. mnorenbe@med.miami.edu.
authors.forename: M D
authors.initials: MD
authors.lastname: Norenberg
mesh_terms: D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010474:Percussion; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005973:Glutamine; D019344:Lactic Acid; D005947:Glucose
keywords: Cell death; GC–MS; Neuron; Oxidative metabolism; Traumatic brain injury