Energy Metabolism in Brain Injury

Background: Ischemic and hypoxic secondary brain insults are common and detrimental in traumatic brain injury (TBI). Treatment aims to maintain an adequate cerebral blood flow with sufficient arterial oxygen content. It has been suggested that arterial hyperoxia may be beneficial to the injured brain to compensate for cerebral ischemia, overcome diffusion barriers, and improve mitochondrial function. In this study, we investigated the relation between arterial oxygen levels and cerebral energy metabolism, pressure autoregulation, and clinical outcome. Methods: This retrospective study was based on 115 patients with severe TBI treated in the neurointensive care unit, Uppsala university hospital, Sweden, 2008 to 2018. Data from cerebral microdialysis (MD), arterial blood gases, hemodynamics, and intracranial pressure were analyzed the first 10 days post-injury. The first day post-injury was studied in particular. Results: Arterial oxygen levels were higher and with greater variability on the first day post-injury, whereas it was more stable the following 9 days. Normal-to-high mean pO2 was significantly associated with better pressure autoregulation/lower pressure reactivity index ( P = .02) and lower cerebral MD-lactate ( P = .04) on day 1. Patients with limited cerebral energy metabolic substrate supply (MD-pyruvate below 120 µM) and metabolic disturbances with MD-lactate-/pyruvate ratio (LPR) above 25 had significantly lower arterial oxygen levels than those with limited MD-pyruvate supply and normal MD-LPR ( P = .001) this day. Arterial oxygenation was not associated with clinical outcome. Conclusions: Maintaining a pO2 above 12 kPa and higher may improve oxidative cerebral energy metabolism and pressure autoregulation, particularly in cases of limited energy substrate supply in the early phase of TBI. Evaluating the cerebral energy metabolic profile could yield a better patient selection for hyperoxic treatment in future trials.

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Systemic Hyperthermia in Traumatic Brain Injury—Relation to Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome

Journal of Neurosurgical Anesthesiology ◽

10.1097/ana.0000000000000695 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Teodor M. Svedung Wettervik ◽

Henrik Engquist ◽

Samuel Lenell ◽

Timothy Howells ◽

Lars Hillered ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Energy Metabolism ◽

Intracranial Pressure ◽

Clinical Outcome ◽

Cerebral Energy Metabolism ◽

Pressure Dynamics

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Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211042112 ◽

2021 ◽

pp. 0271678X2110421

Author(s):

Abdelhakim Khellaf ◽

Nuria Marco Garcia ◽

Tamara Tajsic ◽

Aftab Alam ◽

Matthew G Stovell ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Energy Metabolism ◽

Mitochondrial Dysfunction ◽

Cerebral Metabolism ◽

Tricarboxylic Acid Cycle ◽

Resonance Spectroscopy ◽

Brain Tissue Oxygenation ◽

Clinical Algorithm ◽

Management Protocol

Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral ‘mitochondrial dysfunction’ (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification. Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(−12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.

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Low Molecular Weight Dextran Sulfate (ILB®) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat

Antioxidants ◽

10.3390/antiox9090850 ◽

2020 ◽

Vol 9 (9) ◽

pp. 850

Author(s):

Giacomo Lazzarino ◽

Angela Maria Amorini ◽

Nicholas M. Barnes ◽

Lars Bruce ◽

Alvaro Mordente ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Molecular Weight ◽

Brain Injury ◽

Energy Metabolism ◽

Nitrosative Stress ◽

Dextran Sulfate ◽

Subcutaneous Administration ◽

Water Soluble ◽

Low Molecular Weight ◽

Post Injury

Traumatic brain injury (TBI) is the leading cause of death and disability in people less than 40 years of age in Western countries. Currently, there are no satisfying pharmacological treatments for TBI patients. In this study, we subjected rats to severe TBI (sTBI), testing the effects of a single subcutaneous administration, 30 min post-impact, of a new low molecular weight dextran sulfate, named ILB®, at three different dose levels (1, 5, and 15 mg/kg body weight). A group of control sham-operated animals and one of untreated sTBI rats were used for comparison (each group n = 12). On day 2 or 7 post-sTBI animals were sacrificed and the simultaneous HPLC analysis of energy metabolites, N-acetylaspartate (NAA), oxidized and reduced nicotinic coenzymes, water-soluble antioxidants, and biomarkers of oxidative/nitrosative stress was carried out on deproteinized cerebral homogenates. Compared to untreated sTBI rats, ILB® improved energy metabolism by increasing ATP, ATP/ adenosine diphosphate ratio (ATP/ADP ratio), and triphosphate nucleosides, dose-dependently increased NAA concentrations, protected nicotinic coenzyme levels and their oxidized over reduced ratios, prevented depletion of ascorbate and reduced glutathione (GSH), and decreased oxidative (malondialdehyde formation) and nitrosative stress (nitrite + nitrate production). Although needing further experiments, these data provide the first evidence that a single post-injury injection of a new low molecular weight dextran sulfate (ILB®) has beneficial effects on sTBI metabolic damages. Due to the absence of adverse effects in humans, ILB® represents a promising therapeutic agent for the treatment of sTBI patients.

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Rhodiola crenulata attenuates apoptosis and mitochondrial energy metabolism disorder in rats with hypobaric hypoxia-induced brain injury by regulating the HIF-1α/microRNA 210/ISCU1/2(COX10) signaling pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2019.03.028 ◽

2019 ◽

Vol 241 ◽

pp. 111801 ◽

Cited By ~ 14

Author(s):

Xiaobo Wang ◽

Ya Hou ◽

Qiuyue Li ◽

Xuanhao Li ◽

Wenxiang Wang ◽

...

Keyword(s):

Brain Injury ◽

Energy Metabolism ◽

Signaling Pathway ◽

Hypobaric Hypoxia ◽

Mitochondrial Energy Metabolism ◽

Metabolism Disorder ◽

Rhodiola Crenulata ◽

Energy Metabolism Disorder

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Cerebral energy metabolism following fluid-percussion brain injury in cats

Journal of Neurosurgery ◽

10.3171/jns.1988.68.4.0594 ◽

1988 ◽

Vol 68 (4) ◽

pp. 594-600 ◽

Cited By ~ 73

Author(s):

Andreas W. Unterberg ◽

Bruce J. Andersen ◽

Geoff D. Clarke ◽

Anthony Marmarou

Keyword(s):

Brain Injury ◽

Energy Metabolism ◽

Glucose Consumption ◽

Tissue Ph ◽

Content Type ◽

Cerebral Energy Metabolism ◽

Fluid Percussion ◽

Metabolic Perturbation ◽

Fine Print ◽

Observation Period

✓ Clinical and experimental evidence suggests that head injury can cause alterations of cerebral energy metabolism. However, the etiology of this metabolic perturbation is not known. The objective of this study was to determine the effect of fluid-percussion trauma on cerebral energy metabolism. Seven ventilated, chloralose-anesthetized cats were subjected to a 3.2-atm fluid-percussion brain injury. Before and for 8 hours after trauma, continuous phosphorus-31 magnetic resonance spectrography was obtained to noninvasively monitor tissue pH, phosphocreatine (PCr), and inorganic phosphate (Pi) levels. Measurement of cerebral blood flow (CBF) by the radioactive microsphere technique and calculation of oxygen and glucose consumption (CMRO2 and CMRGl) were also performed before trauma as well as 30 minutes and 1,2,4, and 8 hours after trauma. The data showed a moderate decrease in tissue pH from 7.04 to 6.89 at 30 minutes following trauma with return to control levels by 3 hours posttrauma. During the 8-hour observation period, CBF, CMRO2, and CMRGl remained at control levels. Tissue PCr and Pi levels were also unchanged. Fluid-percussion trauma at the 3.2-atm level in ventilated cats causes a moderate and transient decrease in tissue pH that returns to control levels after trauma. No other metabolic changes are seen later than 30 minutes posttrauma. This indicates that a mild metabolic disturbance occurs after trauma in the ventilated animal and quickly returns to normal.

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