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.

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 The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chung-Che Lu ◽  
Tee-Tau Eric Nyam ◽  
Jinn-Rung Kuo ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glutamate Receptor ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Abstract Background The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). Methods Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. Results The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. Conclusions We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

scholarly journals The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury

2020 ◽  
Author(s):  
Chung-Che Lu ◽  
Che-Chuan Wang ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
Sher-Wei Lim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Neuroprotective Effect ◽  
Acute Stage ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Infarction Volume

Abstract The aim of this study is to investigate whether the neuroprotective effect of AMN082 is via attenuating glutamic receptor associated neuronal apoptosis and improves functional outcomes after traumatic brain injury (TBI). Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 was intraperitoneally injected (10 mg/kg) at 0, 24, and 48 hr after TBI. During the 120 minutes after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. The motor function, infarction volume, and neuronal nitrosative stress-associated apoptosis, N-Methyl-D-aspartate receptor 2A (NR2A) and NR2B expression were measured on the 3rd day after TBI. The results showed AMN082-treated group had the lower ICP and higher CPP after TBI. The TBI-induced motor deficits, increased infarction volume, neuronal apoptosis, 3-nitrotyrosine and inducible nitric oxide synthase expression in the peri-contusion cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased the NR2A and NR2B expression in neuronal cells. We concluded intraperitoneal injection of AMN082 for 3 days may ameliorate TBI insults by attenuating glutamic receptor associated nitrosative stress and neuronal apoptosis in the peri-contusion cortex. We suggest AMN082 administration in acute stage may be a promising strategy for TBI.

Do long-term results justify decompressive craniectomy after severe traumatic brain injury?

2008 ◽  
Vol 109 (4) ◽  
pp. 685-690 ◽  
Author(s):  
Matthias H. Morgalla ◽  
Bernd E. Will ◽  
Florian Roser ◽  
Marcos Tatagiba
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Decompressive Craniectomy ◽  
Severe Traumatic Brain Injury ◽  
Barthel Index ◽  
Case Series ◽  
Clinical Results ◽  
Long Term Results

Object A decompressive craniectomy can be a life-saving procedure to relieve critically increased intracranial pressure. The survival of a patient is important as well as the subsequent and long-term quality of life. In this paper the authors' goal was to investigate whether long-term clinical results justify the use of a decompressive craniectomy. Methods Thirty-three patients (20 males and 13 females) with a mean age of 36.3 years (range 13–60 years) with severe traumatic brain injury (Grades III and IV) and subsequent massive brain swelling were examined. For postoperative assessment the Barthel Index was used. A surgical intervention was based on the following criteria: 1) The intracranial pressure could not be controlled by conservative treatment and constantly exceeded 30 mm Hg (cerebral perfusion pressure < 50 mm Hg). 2) Transcranial Doppler ultrasonography revealed only a systolic flow pattern or systolic peaks. 3) There were no other major injuries. 4) The patient was not older than 60 years. Results One-fifth of all patients died and one-fifth remained in a vegetative state. Mild deficits were seen in 6 of 33 patients. A full rehabilitation (Barthel Index 90–100) was achieved in 13 patients (39.4%). Five patients could resume their former occupation, and another 4 had to change jobs. Conclusions Age remains to be one of the most important exclusion factors. Decompressive craniectomy provided good clinical results in nearly 40% of patients who were otherwise most likely to die. Therefore, long-term results justify the use of decompressive craniectomy in this case series.

N-methyl-D-aspartate preconditioning improves short-term motor deficits outcome after mild traumatic brain injury in mice

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Tayana Costa ◽  
Leandra C. Constantino ◽  
Bruna P. Mendonça ◽  
Josimar G. Pereira ◽  
Bruno Herculano ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Motor Deficits ◽  
Short Term

Reversible monoparesis following decompressive hemicraniectomy for traumatic brain injury

2008 ◽  
Vol 109 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Shirley I. Stiver ◽  
Max Wintermark ◽  
Geoffrey T. Manley
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Motor Function ◽  
Ct Perfusion ◽  
Motor Deficits ◽  
Decompressive Hemicraniectomy ◽  
Number Of Patients ◽  
Motor Strength

Object The “syndrome of the trephined” is an uncommon and poorly understood disorder of delayed neurological deficit following craniectomy. From the authors' extensive experience with decompressive hemicraniectomy for traumatic brain injury (TBI), they have encountered a number of patients who developed delayed motor deficits, also called “motor trephine syndrome,” and reversal of the weakness following cranioplasty repair. The authors set out to study motor function systematically in this patient population to define the incidence, contributing factors, and outcome of patients with motor trephine syndrome. Methods The authors evaluated patient demographics, injury characteristics, detailed motor examinations, and CT scans in 38 patients with long-term follow-up after decompressive hemicraniectomy for TBI. Results Ten patients (26%) experienced delayed contralateral upper-extremity weakness, beginning 4.9 ± 0.4 months (mean ± standard error) after decompressive hemicraniectomy. Motor deficits improved markedly within 72 hours of cranioplasty repair, and all patients recovered full motor function. The CT perfusion scans, performed in 2 patients, demonstrated improvements in cerebral blood flow commensurate with resolution of cerebrospinal fluid flow disturbances on CT scanning and return of motor strength. Comparisons between 10 patients with and 20 patients (53%) without delayed motor deficits identified 3 factors—ipsilateral contusions, abnormal cerebrospinal fluid circulation, and longer intervals to cranioplasty repair—to be strongly associated with delayed, reversible monoparesis following decompressive hemicraniectomy. Conclusions Delayed, reversible monoparesis, also called motor trephine syndrome, is common following decompressive hemicraniectomy for TBI. The results of this study suggest that close follow-up of motor strength with early cranioplasty repair may prevent delayed motor complications of decompressive hemicraniectomy.

Neuroimaging Patterns Associated with Motor Control in Traumatic Brain Injury

2006 ◽  
Vol 20 (1) ◽  
pp. 14-23 ◽  
Author(s):  
M. Lotze ◽  
W. Grodd ◽  
F. A. Rodden ◽  
E. Gut ◽  
P. W. Schönle ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Premotor Cortex ◽  
Blood Oxygenation ◽  
Motor Deficits ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Fmri Signal ◽  
Signal Change ◽  
Motor Areas

Objective. To determine if patients with traumatic brain injury (TBI) and motor deficits show differences in functional activation maps during repetitive hand movements relative to healthy controls. Are there predictors for motor outcome in the functional maps of these patients? Methods. In an exploratory cross-sectional study, functional magnetic resonance imaging (fMRI) was used to study the blood-oxygenation-level-dependent (BOLD) response in cortical motor areas of 34 patients suffering from moderate motor deficits after TBI as they performed unilateral fist-clenching motions. Twelve of these patients with unilateral motor deficits were studied 3 months after TBI and a 2nd time approximately 4 months later. Results. Compared to age-matched, healthy controls performing the same task, TBI patients showed diminished fMRI-signal change in the primary sensorimotor cortex contralateral to the moving hand (cSM1), the contralateral dorsal premotor cortex, and bilaterally in the supplementary motor areas (SMAs). Clinical impairment and the magnitude of the fMRI-signal change in cSM1 and SMA were negatively correlated. Patients with poor and good motor recovery showed comparable motor impairment at baseline. Only patients who evolved to “poor clinical outcome” had decreased fMRI-signal change in the cSM1 during baseline. Conclusions. These observations raise the hypothesis that the magnitude of the fMRI-signal change in the cSM1 region could have prognostic value in the evaluation of patients with TBI.

scholarly journals Attenuation of Brain Nitrostative and Oxidative Damage by Brain Cooling during Experimental Traumatic Brain Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jinn-Rung Kuo ◽  
Chong-Jeh Lo ◽  
Ching-Ping Chang ◽  
Mao- Tsun Lin ◽  
Chung-Ching Chio
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Jugular Vein ◽  
External Jugular Vein ◽  
Motor Deficits ◽  
Sham Operation ◽  
Brain Cooling ◽  
Cerebral Contusion ◽  
Oxide Synthase

The aim of the present study was to ascertain whether brain cooling causes attenuation of traumatic brain injury by reducing brain nitrostative and oxidative damage. Brain cooling was accomplished by infusion of 5 mL of 4°C saline over 5 minutes via the external jugular vein. Immediately after the onset of traumatic brain injury, rats were randomized into two groups and given 37°C or 4°C normal saline. Another group of rats were used as sham operated controls. Behavioral and biochemical assessments were conducted on 72 hours after brain injury or sham operation. As compared to those of the sham-operated controls, the 37°C saline-treated brain injured animals displayed motor deficits, higher cerebral contusion volume and incidence, higher oxidative damage (e.g., lower values of cerebral superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, but higher values of cerebral malondialdehyde), and higher nitrostative damage (e.g., higher values of neuronal nitric oxide synthase and 3-nitrotyrosine). All the motor deficits and brain nitrostative and oxidative damage were significantly reduced by retrograde perfusion of 4°C saline via the jugular vein. Our data suggest that brain cooling may improve the outcomes of traumatic brain injury in rats by reducing brain nitrostative and oxidative damage.

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