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

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

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Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0546 ◽

2015 ◽

Vol 93 (8) ◽

pp. 687-694 ◽

Cited By ~ 26

Author(s):

Alireza Sarkaki ◽

Yaghoub Farbood ◽

Mohammad Kazem Gharib-Naseri ◽

Mohammad Badavi ◽

Mohammad Taghi Mansouri ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Gallic Acid ◽

Brain Tissue ◽

Proinflammatory Cytokines ◽

Repeated Measures ◽

Long Term Potentiation ◽

Tissue Levels ◽

Tnf Α ◽

The Brain

Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou’s method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey’s post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1β, IL-6, and TNF-α. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

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

Brain Sciences ◽

10.3390/brainsci11070889 ◽

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.

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Dynamics of clusterin protein expression in the brain and plasma following experimental traumatic brain injury

Scientific Reports ◽

10.1038/s41598-019-56683-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Shalini Das Gupta ◽

Anssi Lipponen ◽

Kaisa M. A. Paldanius ◽

Noora Puhakka ◽

Asla Pitkänen

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Protein Expression ◽

Fold Increase ◽

Mrna Levels ◽

Sprague Dawley ◽

Post Injury ◽

Fluid Percussion Injury ◽

Clusterin Protein ◽

The Brain

AbstractProgress in the preclinical and clinical development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI) necessitates the discovery of prognostic biomarkers for post-injury outcome. Our previous mRNA-seq data revealed a 1.8–2.5 fold increase in clusterin mRNA expression in lesioned brain areas in rats with lateral fluid-percussion injury (FPI)-induced TBI. On this basis, we hypothesized that TBI leads to increases in the brain levels of clusterin protein, and consequently, increased plasma clusterin levels. For evaluation, we induced TBI in adult male Sprague-Dawley rats (n = 80) by lateral FPI. We validated our mRNA-seq findings with RT-qPCR, confirming increased clusterin mRNA levels in the perilesional cortex (FC 3.3, p < 0.01) and ipsilateral thalamus (FC 2.4, p < 0.05) at 3 months post-TBI. Immunohistochemistry revealed a marked increase in extracellular clusterin protein expression in the perilesional cortex and ipsilateral hippocampus (7d to 1 month post-TBI), and ipsilateral thalamus (14d to 12 months post-TBI). In the thalamus, punctate immunoreactivity was most intense around activated microglia and mitochondria. Enzyme-linked immunoassays indicated that an acute 15% reduction, rather than an increase in plasma clusterin levels differentiated animals with TBI from sham-operated controls (AUC 0.851, p < 0.05). Our findings suggest that plasma clusterin is a candidate biomarker for acute TBI diagnosis.

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

Scientific Reports ◽

10.1038/s41598-020-75479-7 ◽

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.

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Bisleuconothine A potentiates the effect of hyperbaric oxygen therapy against traumatic brain injury by enhancing P2X4 protein expressions

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i2.5 ◽

2020 ◽

Vol 19 (2) ◽

pp. 247-252

Author(s):

Xiangen Meng ◽

Chunyang Zhang ◽

Na Li ◽

Yu Zhang ◽

Danfeng Fan ◽

...

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Hyperbaric Oxygen ◽

Inflammatory Mediators ◽

Traumatic Injury ◽

Neuronal Injury ◽

Sprague Dawley ◽

Protein Expressions ◽

The Brain

Purpose: To investigate the effect of bisleuconothine A (BA), alone and in combination with hyperbaric oxygen (HO), on traumatic brain injury (TBI) in rats. Methods: Traumatic brain injury (TBI) was induced by dropping a 200-g weight of steel on the left anterior frontal areas of Sprague-Dawley rats. The synergistic effect of BA and HO was determined by assessing neurological score, as well as parameters of oxidative stress and inflammation, expressions of P2X4 protein and other proteins, and levels of reactive oxygen species (ROS) in the brain tissues of TBI rats. Results: Neurological function score, levels of inflammatory mediators and oxidative stress parameters were significantly reduced in rats treated with BA alone, and in those treated with a combination of BA and HO, when compared with untreated TBI rats (p < 0.01). Moreover, treatment with BA alone, and BA-HO combination attenuated the altered protein expressions of P2X4, Akt, PI3K and TLR-4 in the TBI rats, and also upregulated the mRNA expression of P2X4 in the brain tissue, when compared with untreated TBI rats (p < 0.01). Conclusion: These results suggest that BA, when used alone or in combination with HO, reduces neuronal injury through upregulation of the protein expression of P2X4 in rats with traumatic brain injury. Thus, BA may be used clinically with HO therapy for the management of traumatic injury. Keywords: Bisleuconothine A, Hyperbaric oxygen, Neuronal injury, Oxidative stress, Inflammatory mediators

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A simple rat model of mild traumatic brain injury: device to reproduce anatomical and neurological changes of mild traumatic brain injury

10.7287/peerj.preprints.2037 ◽

2016 ◽

Author(s):

Ho Jeong Kim ◽

Soo Jeong Han

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Water Pressure ◽

Brain Mri ◽

Free Fall ◽

Absolute Number ◽

Grid Floor ◽

Sprague Dawley ◽

The Brain

Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used the water pressure or rotational injury for designing the device to make a rat mild traumatic brain injury model. The objective of this study was to make a simple model of mild traumatic brain injury in rat. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175g) was freely dropped 30cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague–Dawley rats, we performed the brain magnetic resonance image(MRI) within 24 hours after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. Absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain. But the difference of ratio was lesser than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rat. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9364598 ◽

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.

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A simple rat model of mild traumatic brain injury: a device to reproduce anatomical and neurological changes of mild traumatic brain injury

PeerJ ◽

10.7717/peerj.2818 ◽

2017 ◽

Vol 5 ◽

pp. e2818 ◽

Cited By ~ 4

Author(s):

Ho Jeong Kim ◽

Soo Jeong Han

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Water Pressure ◽

Brain Mri ◽

Free Fall ◽

Absolute Number ◽

Grid Floor ◽

Sprague Dawley ◽

The Brain

Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.

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

Current Pharmaceutical Design ◽

10.2174/1381612825666191111153802 ◽

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.

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Effect of Cerebral Vasculatures on the Mechanical Response of Brain Tissue: A Preliminary Study

10.1115/imece2000-2477 ◽

2000 ◽

Author(s):

Kiyoshi Omori ◽

Liying Zhang ◽

King H. Yang ◽

Albert I. King

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Tissue ◽

Mechanical Response ◽

Clinical Symptoms ◽

Anatomical Structure ◽

Causal Mechanism ◽

Injury Biomechanics ◽

Preliminary Study ◽

The Brain

Abstract Traumatic brain injury (TBI) constitutes a significant portion of all injuries occurring as a result of automotive, motorcycle and sports related injuries. Over the years, a large amount of literature has been devoted to an increased understanding of clinical symptoms, pathological evidence and injury biomechanics for such injuries. However, the precise causal mechanism, which accounts for complex mechanical interactions and responses in an anatomical structure as complex as the brain, is not fully understood.

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