title: Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.
abstract: Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand.
authors.affiliation: UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7039, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Box 957039, Los Angeles, CA 90095-7039, USA. Electronic address: moro.nobuhiro@nihon-u.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Moro
authors.forename: Sima
authors.initials: S
authors.lastname: Ghavim
authors.forename: Neil G
authors.initials: NG
authors.lastname: Harris
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sutton
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D005947:Glucose
keywords: (14)C-2DG; 4′,6-diamidino-2-phenylindol dihydrochloride; 5% dextrose in 0.9% saline; ANLS; ANOVA; ATP; CCI; CMRGlc; CMRO(2); Controlled cortical impact; D5NS; DAPI; FJB; FPI; Fluoro-Jade B; GLC; Hyperglycemia; Mg(++); PBS; ROS; Rat; SAL; SEM; TBI; adenosine triphosphate; analysis of variance; astrocyte-neuron lactate shuttle; cerebral metabolic rates of glucose; cerebral metabolic rates of oxygen; controlled cortical impact; fluid percussion injury; glucose (50%); magnesium; phosphate buffered saline; reactive oxygen species; saline (8%); standard error of the mean; traumatic brain injury