Lactate storm marks cerebral metabolism following brain trauma.
Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure.
From the Department of Clinical Neurosciences and the Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 2T9, Canada and.
Sanju
S
Lama
the Hôpital Ste-Justine, Département de Pathologie, Université de Montréal, Montreal, Québec H3T 1C5, Canada.
Roland N
RN
Auer
From the Department of Clinical Neurosciences and the Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 2T9, Canada and.
Randy
R
Tyson
From the Department of Clinical Neurosciences and the Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 2T9, Canada and.
Clare N
CN
Gallagher
From the Department of Clinical Neurosciences and the Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 2T9, Canada and.
Boguslaw
B
Tomanek
From the Department of Clinical Neurosciences and the Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 2T9, Canada and garnette@ucalgary.ca.
Garnette R
GR
Sutherland
D019342:Acetic Acid / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005904:Glial Fibrillary Acidic Protein; D019344:Lactic Acid; D005947:Glucose; D019342:Acetic Acid
13C-Labeled Substrates; Brain Metabolism; Glial Cell; Lactate; MR Spectroscopy; Neuron; Neuronal-Glial Metabolism; Tau Protein (Tau); Traumatic Brain Injury; Tricarboxylic Acid Cycle (TCA Cycle) (Krebs Cycle)