Ethanol Reduces Metabolic Uncoupling Following Experimental Head Injury

Kelly, Daniel F.; Kozlowski, Dorothy A.; Haddad, Evelyn; Echiverri, Angela; Hovda, David A.; Lee, Stefan M.

doi:10.1089/neu.2000.17.261

Cited by 78 publications

(53 citation statements)

References 71 publications

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“…We believe that this could be because of the use of ethanol as a vehicle, because ethanol has been shown previously to have neuroprotective properties. 28,29 Our study effectively delivered a total of 0.1 g/kg of ethanol to the mice over two administrations. Previous studies have shown that 1 g/kg of ethanol can improve cerebral blood flow and reduce metabolic uncoupling after CCI in mice, 29 and 1.5 g/kg can reduce lesion volume and improve outcome in an ischemia model.…”

Section: Discussionmentioning

confidence: 99%

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Winston

Chellappa

Wilkins

et al. 2013

Journal of Neurotrauma

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The clinical manifestations that occur after traumatic brain injury (TBI) include a wide range of cognitive, emotional, and behavioral deficits. The loss of excitatory synapses could potentially explain why such diverse symptoms occur after TBI, and a recent preclinical study has demonstrated a loss of dendritic spines, the postsynaptic site of the excitatory synapse, after fluid percussion injury. The objective of this study was to determine if controlled cortical impact (CCI) also resulted in dendritic spine retraction and to probe the underlying mechanisms of this spine loss. We used a unilateral CCI and visualized neurons and dendtritic spines at 24 h post-injury using Golgi stain. We found that TBI caused a 32% reduction of dendritic spines in layer II/III of the ipsilateral cortex and a 20% reduction in the dendritic spines of the ipsilateral dentate gyrus. Spine loss was not restricted to the ipsilateral hemisphere, however, with similar reductions in spine numbers recorded in the contralateral cortex (25% reduction) and hippocampus (23% reduction). Amyloid-b (Ab), a neurotoxic peptide commonly associated with Alzheimer disease, accumulates rapidly after TBI and is also known to cause synaptic loss. To determine if Ab contributes to spine loss after brain injury, we administered a c-secretase inhibitor LY450139 after TBI. We found that while LY450139 administration could attenuate the TBI-induced increase in Ab, it had no effect on dendritic spine loss after TBI. We conclude that the acute, global loss of dendritic spines after TBI is independent of c-secretase activity or TBI-induced Ab accumulation.

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Section: Discussionmentioning

confidence: 99%

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Winston

Chellappa

Wilkins

et al. 2013

Journal of Neurotrauma

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“…have suggested that alcohol might have a neuroprotective effect on the brain following traumatic brain injury (TBI) through such mechanisms as inhibiting N-methyl-Daspartate (NMDA) receptor-mediated excitotoxicity (Cebere and Liljequist, 2003;Chandler et al, 1993;Is et al, 2005;Türeci et al, 2004), decreasing the degree of uncoupling between glucose metabolism and cerebral blood fl ow (Kelly et al, 2000), inhibiting the production of pro-infl ammatory cytokines (Gottesfeld et al, 2002), attenuating TBI-induced hyperthermia (Taylor et al, 2002), and blunting the sympathoadrenal response in TBI (Opreanu et al, 2010). Premised on the evidence from animal research, one recent study confi rmed that patients who were intoxicated at the time of injury had better acute neuropsychological outcomes when recovering from TBI than did nonintoxicated patients (Lange et al, 2008).…”

Section: S Everal Animal and Laboratory Studiesmentioning

confidence: 99%

Alcohol Use at Time of Injury and Survival Following Traumatic Brain Injury: Results From the National Trauma Data Bank

Chen¹,

Yi²,

Yoon³

et al. 2012

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Premised on biological evidence from animal research, recent clinical studies have, for the most part, concluded that elevated blood alcohol concentration levels are independently associated with higher survival or decreased mortality in patients with moderate to severe traumatic brain injury (TBI). This study aims to provide some counterevidence to this claim and to further future investigations. Method: Incident data were drawn from the largest U.S. trauma registry, the National Trauma Data Bank, for emergency department admission years [2002][2003][2004][2005][2006]. TBI was identifi ed according to the National Trauma Data Bank's defi nition using International Classifi cation of Diseases, Ninth Revision, Clinical Modifi cation (ICD-9-CM), codes. To eliminate confounding, the exact matching method was used to match alcohol-positive with alcohol-negative incidents on sex, age, race/ethnicity, and facility. Logistic regression compared in-hospital mortality between 44,043 alcohol-positive and 59,817 matched alcohol-negative TBI incidents, with and without causes and intents of TBI and Injury Severity Score as covariates. A sensitivity analysis was performed within a subsample of isolated moderate to severe TBI incidents. Results: Alcohol use at the time of injury was found to be signifi cantly associated with an increased risk for TBI. Including varied causes and intents of TBI and Injury Severity Score as potential confounders in the regression model explained away the statistical signifi cance of the seemingly protective effect of alcohol against TBI mortality for all TBIs and for isolated moderate to severe TBIs. Conclusions: The null fi nding shows that the purported reduction in TBI mortality attributed to positive blood alcohol likely is attributable to residual confounding. Accordingly, the risk of TBI associated with alcohol use should not be overlooked. (J. Stud. Alcohol Drugs, 73, 531-541, 2012)

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“…The previously characterized CCI injury device (Sutton et al, 1993;Lindner et al, 1998;Kelly et al, 2000) was used to generate a cortical contusion to the left hemisphere. Each animal was placed under inhalation anesthesia with isoflurane (4% for induction, 2.0% for maintenance, in 100% O 2 at 1.5 l/min).…”

Section: Injurymentioning

confidence: 99%

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

et al. 2008

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Prior work has shown that d-amphetamine (AMPH) treatment or voluntary exercise improves cognitive functions after traumatic brain injury (TBI). In addition, voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF). The current study was conducted to determine how AMPH and exercise treatments, either alone or in combination, affect molecular events that may underlie recovery following controlled cortical impact (CCI) injury in rats. We also determined if these treatments reduced injury-induced oxidative stress. Following a CCI or sham injury, rats received AMPH (1 mg/kg/day) or saline treatment via an ALZET ® pump and were housed with or without access to a running wheel for 7 days. CCI rats ran significantly less than sham controls, but exercise level was not altered by drug treatment. On day 7 the hippocampus ipsilateral to injury was harvested and BDNF, synapsin I and phosphorylated (P) -synapsin I proteins were quantified. Exercise or AMPH alone significantly increased BDNF protein in sham and CCI rats, but this effect was lost with the combined treatment. In sham-injured rats synapsin I increased significantly after AMPH or exercise, but did not increase after combined treatment. Synapsin levels, including the Psynapsin/total synapsin ratio, were reduced from sham controls in the saline-treated CCI groups, with or without exercise. AMPH treatment significantly increased the P-synapsin/total synapsin ratio after CCI, an effect that was attenuated by combining AMPH with exercise. Exercise or AMPH treatment alone significantly decreased hippocampal carbonyl groups on oxidized proteins in the CCI rats, compared with saline-treated sedentary counterparts, but this reduction in a marker of oxidative stress was not found with the combination of exercise and AMPH treatment. These results indicate that, whereas exercise or AMPH treatment alone may induce plasticity and reduce oxidative stress after TBI, combining these treatments may cancel each other's therapeutic effects. Keywordscontrolled cortical impact; norepinephrine; oxidized proteins; running wheel; traumatic brain injury *Corresponding author. Tel: +1-310-825-1904; fax: +1-310-794-2147. E-mail address: ggriesbach@mednet.ucla.edu (G. S. Griesbach). 1 G.S.G. and R.L.S. contributed equally to this work. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 June 27. Published in final edited form as:Neuroscience. 2008 June 23; 154(2): 530-540. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTraumatic brain injury (TBI) continues to be one of the leading causes of mortality and morbidity, with approximately 5.3 million Americans suffering from enduring disabilities resulting from TBI (Binder et al., 2005). Despite many experimental and clinical efforts using numerous therapeutic approaches, there are currently no proven treatments to alleviate the sequelae of TBI or to enhance recovery of function.Our laboratories have been investigating treatment strategies that may faci...

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Ethanol Reduces Metabolic Uncoupling Following Experimental Head Injury

Cited by 78 publications

References 71 publications

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Alcohol Use at Time of Injury and Survival Following Traumatic Brain Injury: Results From the National Trauma Data Bank

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

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