scholarly journals Mitochondrial-Protective Effects of R-Phenibut after Experimental Traumatic Brain Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Einars Kupats ◽  
Gundega Stelfa ◽  
Baiba Zvejniece ◽  
Solveiga Grinberga ◽  
Edijs Vavers ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Aminobutyric Acid ◽  
Drug Candidate ◽  
H2o2 Production ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
The Impact ◽  
The Brain

Altered neuronal Ca2+ homeostasis and mitochondrial dysfunction play a central role in the pathogenesis of traumatic brain injury (TBI). R-Phenibut ((3R)-phenyl-4-aminobutyric acid) is an antagonist of the α2δ subunit of voltage-dependent calcium channels (VDCC) and an agonist of gamma-aminobutyric acid B (GABA-B) receptors. The aim of this study was to evaluate the potential therapeutic effects of R-phenibut following the lateral fluid percussion injury (latFPI) model of TBI in mice and the impact of R- and S-phenibut on mitochondrial functionality in vitro. By determining the bioavailability of R-phenibut in the mouse brain tissue and plasma, we found that R-phenibut (50 mg/kg) reached the brain tissue 15 min after intraperitoneal (i.p.) and peroral (p.o.) injections. The maximal concentration of R-phenibut in the brain tissues was 0.6 μg/g and 0.2 μg/g tissue after i.p. and p.o. administration, respectively. Male Swiss-Webster mice received i.p. injections of R-phenibut at doses of 10 or 50 mg/kg 2 h after TBI and then once daily for 7 days. R-Phenibut treatment at the dose of 50 mg/kg significantly ameliorated functional deficits after TBI on postinjury days 1, 4, and 7. Seven days after TBI, the number of Nissl-stained dark neurons (N-DNs) and interleukin-1beta (IL-1β) expression in the cerebral neocortex in the area of cortical impact were reduced. Moreover, the addition of R- and S-phenibut at a concentration of 0.5 μg/ml inhibited calcium-induced mitochondrial swelling in the brain homogenate and prevented anoxia-reoxygenation-induced increases in mitochondrial H2O2 production and the H2O2/O ratio. Taken together, these results suggest that R-phenibut could serve as a neuroprotective agent and promising drug candidate for treating TBI.

scholarly journals Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats

2021 ◽  
Vol 11 (7) ◽  
pp. 889
Author(s):  
Anton D. Filev ◽  
Denis N. Silachev ◽  
Ivan A. Ryzhkov ◽  
Konstantin N. Lapin ◽  
Anastasiya S. Babkina ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Target Genes ◽  
Neural Function ◽  
Stress Genes ◽  
Expression Of Genes ◽  
Delayed Recovery ◽  
The Brain ◽  
Lower Expression

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

Traumatic Brain Injury: The Silent Epidemic

1992 ◽  
Vol 3 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Kathy Coburn
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
National Database ◽  
Assessment Practices ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Acute Health Care ◽  
Focal Injury ◽  
The Impact ◽  
The Brain

It is difficult to accurately determine the number of people affected annually by the devastating effects of traumatic brain injury. It is clear, however, that the impact of traumatic brain injury exceeds the financial cost of acute health care. The long-term outcome of patients with traumatic brain injury has been targeted specifically for improvement during this decade. The initial brain injury—known as the primary injury—may occur in one area of the brain (focal injury) or may affect the entire brain (diffuse injury). The outcome depends on many factors, including the severity of the brain injury and the effectiveness of the interventions received. Accurate assessment of the scope of the problem would be improved by the development of a national database and the standardization of assessment practices. Critical care nurses can contribute skill and knowledge in the care of patients with traumatic brain injury and in efforts to prevent the accidents and violence that cause traumatic brain injury

Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury

2013 ◽  
Vol 554 ◽  
pp. 156-161 ◽  
Author(s):  
Yu Okuma ◽  
Feifei Wang ◽  
Atsuhiko Toyoshima ◽  
Masahiro Kameda ◽  
Tomohito Hishikawa ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Therapeutic Effects ◽  
The Brain

scholarly journals Decompressive craniectomy of post-traumatic brain injury: an in silico modelling approach for intracranial hypertension management

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chryso Lambride ◽  
Nicolas Christodoulou ◽  
Anna Michail ◽  
Vasileios Vavourakis ◽  
Triantafyllos Stylianopoulos
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Brain Tissue ◽  
Decompressive Craniectomy ◽  
In Silico ◽  
Pressure Loading ◽  
Post Traumatic ◽  
The Brain

Abstract Traumatic brain injury (TBI) causes brain edema that induces increased intracranial pressure and decreased cerebral perfusion. Decompressive craniectomy has been recommended as a surgical procedure for the management of swollen brain and intracranial hypertension. Proper location and size of a decompressive craniectomy, however, remain controversial and no clinical guidelines are available. Mathematical and computational (in silico) models can predict the optimum geometric conditions and provide insights for the brain mechanical response following a decompressive craniectomy. In this work, we present a finite element model of post-traumatic brain injury and decompressive craniectomy that incorporates a biphasic, nonlinear biomechanical model of the brain. A homogenous pressure is applied in the brain to represent the intracranial pressure loading caused by the tissue swelling and the models calculate the deformations and stresses in the brain as well as the herniated volume of the brain tissue that exits the skull following craniectomy. Simulations for different craniectomy geometries (unilateral, bifrontal and bifrontal with midline bar) and sizes are employed to identify optimal clinical conditions of decompressive craniectomy. The reported results for the herniated volume of the brain tissue as a function of the intracranial pressure loading under a specific geometry and size of craniectomy are exceptionally relevant for decompressive craniectomy planning.

scholarly journals Can Therapeutic Hypothermia Diminish the Impact of Traumatic Brain Injury in Drosophila melanogaster?

2019 ◽  
Vol 13 ◽  
pp. 117906951882485 ◽  
Author(s):  
Shan Lateef ◽  
Aubrie Holman ◽  
Jessica Carpenter ◽  
Jennifer James
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Risk Ratio ◽  
Chronic Traumatic Encephalopathy ◽  
Survival Curve ◽  
Categorical Variables ◽  
Continuous Variables ◽  
The Impact ◽  
The Brain

Background/main objectives: No effective strategy exists to treat the well-recognized, devastating impact of traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE), which is the brain degeneration likely caused by repeated head trauma. The goals of this project were (1) to study the effects of single and recurrent TBI (rTBI) on Drosophila melanogaster’s (a) life span, (b) response to sedatives, and (c) behavioral responses to light and gravity and (2) to determine whether therapeutic hypothermia can mitigate the deleterious effects of TBI. Methods: Five experimental groups were created: (1) control, (2) single TBI or concussion; (3) concussion + hypothermia, (4) rTBI, and (5) rTBI + hypothermia. A “high-impact trauma” (HIT) device was built, which used a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the brain. Hypothermia groups were cooled to 15°C for 3 minutes. Group differences were analyzed with chi-square tests for the categorical variables and with ANOVA tests for the continuous variables. Results: Survival curve analysis showed that rTBI can decrease Drosophila lifespan and hypothermia diminished this impact. Average sedation time for control vs concussion vs concussion + hypothermia was 78 vs 52 vs 61 seconds ( P < .0001). Similarly, rTBI vs rTBI/hypothermia groups took 43 vs 59 seconds ( P < .0001). Concussed flies preferred dark environments compared with control flies (risk ratio 3.3, P < .01) while flies who were concussed and cooled had a risk ratio of 2.7 ( P < .01). Flies with rTBI were almost 4 times likely to prefer the dark environment but only 3 times as likely if they were cooled, compared with controls. Geotaxis was significantly affected by rTBI only and yet less so if rTBI flies were cooled. Conclusions: Hypothermia successfully mitigated many deleterious effects of single TBI and rTBI in Drosophila and may represent a promising breakthrough in the treatment of human TBI.

scholarly journals Apoptotic and Antiapoptotic Mechanisms after Traumatic Brain Injury

2001 ◽  
Vol 21 (10) ◽  
pp. 1189-1198 ◽  
Author(s):  
Robert W. Keane ◽  
Susan Kraydieh ◽  
George Lotocki ◽  
Ofelia F. Alonso ◽  
Phillip Aldana ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protective Role ◽  
Current Data ◽  
Caspase 8 ◽  
Effector Caspase ◽  
Moderate Traumatic Brain Injury ◽  
Apoptotic Pathways ◽  
The Impact ◽  
The Brain

Caspase and inhibitor of apoptosis (IAP) expression was examined in rats subjected to moderate traumatic brain injury (TBI) using a parasagittal fluid-percussion brain insult (1.7 to 2.2 atm). Within 1 hour after injury, caspase-8 and −9, two initiators of apoptosis, were predominantly expressed in superficial cortical areas adjacent to the impact site and in the thalamus. Caspase-3, an effector caspase, was evident at 6 hours throughout the traumatized cerebral cortex and hippocampus. Moreover, the authors observed that XIAP, cIAP-1, and cIAP-2, members of the IAP family, were constitutively expressed in the brain. Colocalization of XIAP-immunolabled cells with cell-specific markers indicated that XIAP is expressed within neurons and a subpopulation of oligodendrocytes. Immunoblots of brain extracts revealed that the processed forms of caspase-8, −9, and −3 are present as early as 1 hour after trauma. The appearance of activated caspases corresponded with the detection of cleavage of XIAP into fragments after injury and a concomitant increase in the levels of cIAP-1 and cIAP-2 in the traumatized hemispheres. The current data are consistent with the hypotheses that caspases in both the extrinsic and intrinsic apoptotic pathways are activated after moderate TBI and that IAPs may have a protective role within the brain with alterations in levels and cleavage of IAPs that contribute to cell death in this setting.

scholarly journals Hericium erinaceus and Coriolus versicolor Modulate Molecular and Biochemical Changes after Traumatic Brain Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 898
Author(s):  
Ramona D’Amico ◽  
Angela Trovato Salinaro ◽  
Roberta Fusco ◽  
Marika Cordaro ◽  
Daniela Impellizzeri ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oral Treatment ◽  
Coriolus Versicolor ◽  
Strong Increase ◽  
Functional Impairments ◽  
Physical Force ◽  
Hericium Erinaceus ◽  
The Impact ◽  
The Brain

Traumatic brain injury (TBI) is a major health and socioeconomic problem affecting the world. This condition results from the application of external physical force to the brain which leads to transient or permanent structural and functional impairments. TBI has been shown to be a risk factor for neurodegeneration which can lead to Parkinson’s disease (PD) for example. In this study, we wanted to explore the development of PD-related pathology in the context of an experimental model of TBI and the potential ability of Coriolus versicolor and Hericium erinaceus to prevent neurodegenerative processes. Traumatic brain injury was induced in mice by controlled cortical impact. Behavioral tests were performed at various times: the animals were sacrificed 30 days after the impact and the brain was processed for Western blot and immunohistochemical analyzes. After the head injury, a significant decrease in the expression of tyrosine hydroxylase and the dopamine transporter in the substantia nigra was observed, as well as significant behavioral alterations that were instead restored following daily oral treatment with Hericium erinaceus and Coriolus versicolor. Furthermore, a strong increase in neuroinflammation and oxidative stress emerged in the vehicle groups. Treatment with Hericium erinaceus and Coriolus versicolor was able to prevent both the neuroinflammatory and oxidative processes typical of PD. This study suggests that PD-related molecular events may be triggered on TBI and that nutritional fungi such as Hericium erinaceus and Coriolus versicolor may be important in redox stress response mechanisms and neuroprotection, preventing the progression of neurodegenerative diseases such as PD.

scholarly journals Analysis of the Histopathology, TNF-α of Microglia Cells Expression, NRG-1/erbB Oligodendrocyte, and Ki67/Apoptosis of Dentate Gyrus Rattus novergicus Brain After Acute Traumatic Brain Injury

2017 ◽  
Vol 6 (1) ◽  
pp. 20
Author(s):  
Wibi Riawan ◽  
Putri Fitri Alfiantya ◽  
Oktavia Rahayu Adianingsih ◽  
Zulkarnaen Zulkarnaen ◽  
Alif Fariz Jazmi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Brain Tissue ◽  
Microscopic Observation ◽  
Pyramidal Cells ◽  
Adult Brain ◽  
Sprague Dawley ◽  
Tnf Α ◽  
The Brain

Head trauma or traumatic brain injury (TBI) gives most serious impact on the central nervous system. Several experimental models have been established to mimic different pathogenesis characteristics of TBI. The purpose of this study was to determine whether there is evidence of hystopathological lesions in the brain tissue after Marmorou TBI models. This study uses Rattus norvegicus Sprague Dawley strain. Macroscopic and microscopic observations on the brain tissue were done. Macroscopic lesions were observed in the brain. Microscopic observation was performed with Haematoxylin-Eosin (HE) staining and immunohistochemistry on the distribution of microglia cells and pyramidal cells in the cortex. Meanwhile, the distribution of NRG-1/ErbB, proliferation, and apoptosis were observed in the hippocampus. The results of macroscopic observation showed that there were wounds caused by falling loads and vasodilatation. On microscopic observation, the TBI group showed an increase in neutrophils distribution and distribution of activated microglia to produce TNF-α, and decrease in the number of cortical pyramidal cells significantly. The distribution of NRG-1 tended to decrease after exposure of TBI and had no effect on its receptor, erbB. Exposure of TBI appears to lower the activity of neuronal cells proliferation in dentate gyrus (DG) area and significantly increase the number of apoptotic cells. Marmarou model is a physiological model of TBI that spontaneously occurs following a trauma to the head, for example trauma due to an accident. This data can be used as a preliminary data of inflammation and tissue regeneration of disrupted adult brain. Therefore, this research could be used as the basis in the studies of therapeutic agents in the process of neurogenesis of brain cells.Keywords: traumatic brain injury, ERG-1/ErbB, dentate gyrus, Ki67, TNF-a, microglia

New Insights into Oxidative Damage and Iron Associated Impairment in Traumatic Brain Injury

2020 ◽  
Vol 25 (45) ◽  
pp. 4737-4746
Author(s):  
Nicolas Toro-Urrego ◽  
Liliana F. Turner ◽  
Marco F. Avila-Rodriguez
Keyword(s):  
Reactive Oxygen Species ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Brain Tissue ◽  
Reactive Oxygen ◽  
Iron Chelators ◽  
Oxygen Species ◽  
Underlying Mechanisms ◽  
The Brain

: Traumatic Brain Injury is considered one of the most prevalent causes of death around the world; more than seventy millions of individuals sustain the condition per year. The consequences of traumatic brain injury on brain tissue are complex and multifactorial, hence, the current palliative treatments are limited to improve patients’ quality of life. The subsequent hemorrhage caused by trauma and the ongoing oxidative process generated by biochemical disturbances in the in the brain tissue may increase iron levels and reactive oxygen species. The relationship between oxidative damage and the traumatic brain injury is well known, for that reason, diminishing factors that potentiate the production of reactive oxygen species have a promissory therapeutic use. Iron chelators are molecules capable of scavenging the oxidative damage from the brain tissue and are currently in use for ironoverload- derived diseases. : Here, we show an updated overview of the underlying mechanisms of the oxidative damage after traumatic brain injury. Later, we introduced the potential use of iron chelators as neuroprotective compounds for traumatic brain injury, highlighting the action mechanisms of iron chelators and their current clinical applications.

A Study on the Impact of Helmet Padding Materials on the Brain Pressure Under Shock Loads

2012 ◽  
Author(s):  
Mehdi Salimi Jazi ◽  
Asghar Rezaei ◽  
Ghodrat Karami ◽  
Fardad Azarmi ◽  
Mariusz Ziejewski
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Vehicle ◽  
Human Head ◽  
Motor Vehicle Crashes ◽  
Ballistic Impacts ◽  
Common Causes ◽  
The Impact ◽  
The Brain ◽  
Brain Pressure

A traumatic brain injury (TBI) can occur from a sharp strain, or acceleration, to the human head. Based on the level of injury, TBIs are classified as mild, moderate, or severe, with the most common causes being motor vehicle crashes; violence related injuries; collisions in sports; and falls are the most common causes of TBIs for the general public. Many soldiers experience a TBI in combat zones when they are exposed to the shock waves from blasts, or to ballistic impacts.

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