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

Antioxidants ◽  
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.

scholarly journals Arterial Oxygenation in Traumatic Brain Injury—Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome

2020 ◽  
pp. 088506662094409
Author(s):  
Teodor Svedung Wettervik ◽  
Henrik Engquist ◽  
Timothy Howells ◽  
Samuel Lenell ◽  
Elham Rostami ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Energy Metabolism ◽  
Clinical Outcome ◽  
Arterial Oxygen ◽  
Arterial Oxygenation ◽  
Post Injury ◽  
Cerebral Energy Metabolism ◽  
Oxygen Levels ◽  
Pressure Autoregulation

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.

Progression of Intracranial Hemorrhage After Chemical Prophylaxis Using Low-Molecular-Weight Heparin in Patients With Traumatic Brain Injury

2021 ◽  
pp. 000313482110540
Author(s):  
Zachary T. Thier ◽  
Kelan Drake-Lavelle ◽  
Phillip J. Prest ◽  
Mark A. Jones ◽  
Jeremy M. Reeves ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Molecular Weight ◽  
Brain Injury ◽  
Intracranial Hemorrhage ◽  
Clinical Management ◽  
Low Molecular Weight Heparin ◽  
Radiographic Progression ◽  
Pupillary Response ◽  
Low Molecular Weight ◽  
Chemical Prophylaxis

Introduction Chemical prophylaxis using low-molecular-weight heparin (LMWH) is considered a standard of care for venous thromboembolism in trauma patients. Our center performs a head computed tomography (CT) scan 24 hours after initiation with prophylactic LMWH in the setting of a known traumatic brain injury (TBI). The purpose was to determine the overall incidence of ICH progression after chemoprophylaxis in patients with a TBI. Methods This retrospective study was performed at a Level I trauma center, from 1/1/2014 to 12/31/2017. Study patients were drawn from the institution’s trauma registry based on Abbreviated Injury Score codes. Results 778 patients met all inclusion criteria after initial chart review. The proportion of patients with an observed radiographic progression of intracranial hemorrhage after LMWH was 5.8%. 3.1% of patients had a change in clinical management. Observed radiographic progression after LMWH prophylaxis and the presence of SDH on initial CT, the bilateral absence of pupillary response in the emergency department, and a diagnosis of dementia were found to have statistically significant correlation with bleed progression after LMWH was initiated. Conclusion Over a 4-year period, the use of CT to evaluate for radiographic progression of traumatic intracranial hemorrhage 24 hours after receiving LMWH resulted in a change in clinical management for 3.1% of patients. The odds of intracranial hemorrhage progression were approximately 6.5× greater in patients with subdural hemorrhage on initial CT, 3.1× greater in patients with lack of bilateral pupillary response in ED, and 4.2× greater in patients who had been diagnosed with dementia.

scholarly journals Antioxidant Therapies in Traumatic Brain Injury

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 260 ◽  
Author(s):  
Valentina Di Pietro ◽  
Kamal M. Yakoub ◽  
Giuseppe Caruso ◽  
Giacomo Lazzarino ◽  
Stefano Signoretti ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Nitrosative Stress ◽  
Clinical Results ◽  
Motor Deficits ◽  
Low Molecular Weight ◽  
Experimental Conditions ◽  
Large Variability ◽  
Routes Of Administration ◽  
Cellular Defenses

Due to a multiplicity of causes provoking traumatic brain injury (TBI), TBI is a highly heterogeneous pathology, characterized by high mortality and disability rates. TBI is an acute neurodegenerative event, potentially and unpredictably evolving into sub-chronic and chronic neurodegenerative events, with transient or permanent neurologic, cognitive, and motor deficits, for which no valid standardized therapies are available. A vast body of literature demonstrates that TBI-induced oxidative/nitrosative stress is involved in the development of both acute and chronic neurodegenerative disorders. Cellular defenses against this phenomenon are largely dependent on low molecular weight antioxidants, most of which are consumed with diet or as nutraceutical supplements. A large number of studies have evaluated the efficacy of antioxidant administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. Points of weakness of preclinical studies are represented by the large variability in the TBI model adopted, in the antioxidant tested, in the timing, dosages, and routes of administration used, and in the variety of molecular and/or neurocognitive parameters evaluated. The analysis of the very few clinical studies does not allow strong conclusions to be drawn on the real effectiveness of antioxidant administration to TBI patients. Standardizing TBI models and different experimental conditions, as well as testing the efficacy of administration of a cocktail of antioxidants rather than only one, should be mandatory. According to some promising clinical results, it appears that sports-related concussion is probably the best type of TBI to test the benefits of antioxidant administration.

Low-molecular-weight heparin versus unfractionated heparin in pediatric traumatic brain injury

2021 ◽  
pp. 1-6
Author(s):  
Inge A. van Erp ◽  
Apostolos Gaitanidis ◽  
Mohamad El Moheb ◽  
Haytham M. A. Kaafarani ◽  
Noelle Saillant ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Molecular Weight ◽  
Brain Injury ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Pediatric Patients ◽  
Low Molecular Weight ◽  
Improvement Program ◽  
Vte Prophylaxis ◽  
Pediatric Tbi

OBJECTIVEThe incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has increased significantly. The Eastern Association for the Surgery of Trauma recommends using low-molecular-weight heparin (LMWH) over unfractionated heparin (UH) in pediatric patients requiring VTE prophylaxis, although this strategy is unsupported by the literature. In this study, the authors compare the outcomes of pediatric TBI patients receiving LMWH versus UH.METHODSThe authors performed a 4-year (2014–2017) analysis of the pediatric American College of Surgeons Trauma Quality Improvement Program. All trauma patients (age ≤ 18 years) with TBI requiring thromboprophylaxis with UH or LMWH were potentially eligible for inclusion. Patients who had been transferred, had died in the emergency department, or had penetrating trauma were excluded. Patients were stratified into either the LMWH or the UH group on the basis of the prophylaxis they had received. Patients were matched on the basis of demographics, injury characteristics, vital signs, and transfusion requirements using propensity score matching (PSM). The study endpoints were VTE, death, and craniotomy after initiation of prophylaxis. Univariate analysis was performed after PSM to compare outcomes.RESULTSA total of 2479 patients met the inclusion criteria (mean age 15.5 ± 3.7 years and 32.0% female), of which 1570 (63.3%) had received LMWH and 909 (36.7%) had received UH. Before PSM, patients receiving UH were younger, had a lower Glasgow Coma Scale score, and had a higher Injury Severity Score. Patients treated in pediatric hospitals were more likely to receive UH (12.9% vs 9.0%, p < 0.001) than patients treated in adult hospitals. Matched patients receiving UH had a higher incidence of VTE (5.1% vs 2.9%, p = 0.03).CONCLUSIONSLMWH prophylaxis in pediatric TBI appears to be more effective than UH in preventing VTE. Large, multicenter prospective studies are warranted to confirm the superiority of LMWH over UH in pediatric patients with TBI. Moreover, outcomes of VTE prophylaxis in the very young remain understudied; therefore, dedicated studies to evaluate this population are needed.

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