scholarly journals Effects of α‑tocopherol and ascorbic acid in the severity and management of traumatic brain injury in albino rats

2013 ◽  
Vol 04 (03) ◽  
pp. 292-297 ◽  
Author(s):  
Gaafar M Ishaq ◽  
Yusuf Saidu ◽  
Lawal S Bilbis ◽  
Suleiman A Muhammad ◽  
Nasir Jinjir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Brain Injury ◽  
Brain Tissue ◽  
Closed Head Injury ◽  
Albino Rats ◽  
Post Injury ◽  
Chain Reactions

ABSTRACT Background: Traumatic brain injury (TBI) is accompanied by substantial accumulation of biomarkers of oxidative stress and depletion of antioxidants reserve which initiate chain reactions that damage brain cells. The present study investigated the role of ascorbic acid and α-tocopherol on the severity and management of TBI in rats. Materials and Methods: Wistar rats were subjected to closed head injury using an accelerated impact device. Rats were administered 45 mg/kg and 60 mg/kg body weight of ascorbic acid, α-tocopherol or a combination of the two vitamins for 2 weeks pre- and post injury. Blood and brain tissue homogenates were analyzed for vitamin C, vitamin E, malondialdehyde, superoxide dismutase, and creatine kinase activities. Results: The results indicated that TBI caused significant (P < 0.05) decreased in vitamins C and E levels in the blood and brain tissue of TBI-untreated rats. The activities of superoxide dismutase in TBI rats were markedly reduced when compared with non traumatized control and showed a tendency to increased following supplementation with vitamins C and E. Supplementation of the vitamins significantly (P < 0.05) reduced malondialdehyde in the treatment groups compared with the TBI-untreated group. Conclusion: The study indicated that pre and post treatment with ascorbic acid and α-tocopherol reduced oxidative stress induced by brain injury and effectively reduced mortality rate in rats.

scholarly journals A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury

2017 ◽  
Vol 38 (10) ◽  
pp. 1818-1827 ◽  
Author(s):  
Raghavendar Chandran ◽  
TaeHee Kim ◽  
Suresh L Mehta ◽  
Eshwar Udho ◽  
Vishal Chanana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Function ◽  
Neurological Dysfunction ◽  
Vehicle Group ◽  
Lesion Volume ◽  
Post Injury ◽  
Cortical Contusion ◽  
Nrf2 Activator

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice. Genetic deletion of NOX2 improved, while Nrf2 worsened the post-TBI motor function recovery and lesion volume indicating that decreasing ROS levels might be beneficial after TBI. Treatment with either apocynin (NOX2 inhibitor) or TBHQ (Nrf2 activator) alone significantly improved the motor function after TBI, but had no effect on the lesion volume, compared to vehicle control. Whereas, the combo therapy (apocynin + TBHQ) given at either 5 min/24 h or 2 h/24 h improved motor and cognitive function and decreased cortical contusion volume compared to vehicle group. Thus, both the generation and disposal of ROS are important modulators of oxidative stress, and a combo therapy that prevents ROS formation and potentiates ROS disposal concurrently is efficacious after TBI.

scholarly journals Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

2019 ◽  
Author(s):  
Christine Smothers ◽  
Chris Winkelman ◽  
Grant C. O’Connell
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Brain Injury ◽  
Brain Tissue ◽  
Tissue Sample ◽  
Surrogate Marker ◽  
Final Analysis ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Original Analysis

AbstractBackgroundDetection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility for use as TBI biomarkers in the acute phase of care.MethodsPublically-available microarray data generated from 31 postmortem human tissues was used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top five ranked miRNAs were then prospectively measured in serum samples collected from 10 TBI patients at hospital admission, as well as from 10 controls.ResultsThe top five miRNAs identified in our analysis (miR-137, miR-219a-5p, miR-128-3p, miR-124-3p, and miR-138-5p) exhibited 31 to 74-fold higher expression in brain relative to other tissues. Furthermore, their levels were elevated in serum from TBI patients compared to controls, and were collectively able to discriminate between groups with 90% sensitivity and 80% specificity. Subsequent informatic pathway analysis revealed that their target transcripts were significantly enriched for components of signaling pathways which are active in peripheral organs such as the heart.ConclusionsThe five candidate miRNAs identified in this study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury.A FINAL PEER REVIEWED VERSION OF THIS ARTICLE HAS BEEN PUBLISHED IN BRAIN INJURY AT THE FOLLOWING DOI: 10.1080/02699052.2020.1764102There are some notable differences between the analysis presented in this preprint and our final peer-reviewed article. There was a single tissue sample originating from spinal cord that we had classified as a non-brain tissue in our original analysis outlined in this preprint. Because the composition of spinal cord and brain are highly similar in terms of gene expression, classifying this sample as a non-brain tissue dramatically reduced the levels of brain enrichment observed in the analysis. Because brain and spinal cord are molecularly highly similar, but technically distinct anatomical structures, we simply decided to exclude this sample from our final analysis published in Brain Injury to avoid confounds. The top 5 miRNAs identified in our original analysis still fell within the top 7 of this final analysis. In addition, the final analysis identified two additional miRNAs which could be candidate biomarkers based on levels of brain enrichment.The final article published in Brain Injury also reports an additional confirmatory tissue specificity analysis performed in a second independent dataset, as well as additional analysis examining the brain specificity of several notable previously proposed miRNA TBI biomarkers, which is not described in this preprint.

scholarly journals The level of oxidative stress in rat brain tissue after a brain trauma injury with introduction of synthetic regulatory peptides

2020 ◽  
pp. 65-67
Author(s):  
A. A. Kolesnikova ◽  
M. Yu. Fleishman ◽  
N. Yu. Yakusheva ◽  
E. V. Slobodenyuk ◽  
I. V. Tolstenok
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Regulatory Peptides ◽  
Antioxidant Effect ◽  
Male Rats ◽  
The Third ◽  
Trauma Injury ◽  
Experimental Traumatic Brain Injury

Objective: Comparative evaluation of the effect of regulatory peptides on lipid peroxidation in brain tissue after traumatic brain injury (TBI).Methods: Reproductive Wistar male rats were divided into 3 groups: the first group received 0.1 mg/kg of “Selang” peptide solution (Thy-Lys-Pro-Arg-Pro-Gly-Pro) within 5 days after the experimental traumatic brain injury, the second group received 0.1 mg/kg AGAPGP peptide (Arg-Gly-Arg-Pro-Gly-Pro), the third (control) – 0.9% sodium chloride solution. Drugs were administered retroperitoneally.Results: According to chemiluminescence in the biomaterial taken from rats of the first group, indicators of oxidative stress were less pronounced.Conclusions: The Selang has a more pronounced antioxidant effect on brain tissue after traumatic brain injury compared with the AGAPGP peptide. 

scholarly journals Ketogenic Diet as a potential treatment for traumatic brain injury in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meirav Har-Even ◽  
Vardit Rubovitch ◽  
Whitney A. Ratliff ◽  
Bar Richmond-Hacham ◽  
Bruce A. Citron ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Ketogenic Diet ◽  
Cognitive Abilities ◽  
Ketone Bodies ◽  
Temporal Cortex ◽  
Closed Head Injury ◽  
Standard Diet ◽  
Post Injury

AbstractTraumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed ketogenic diet (KD) perform better in learning tasks than those fed standard diet (SD) following brain injury. The goal of this study was to examine whether KD is a neuroprotective in TBI mouse model. We utilized a closed head injury model to induce TBI in mice, followed by up to 30 days of KD/SD. Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y-maze and Novel Object Recognition tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating TBI.

scholarly journals New lymphatic cell formation is associated with damaged brain tissue clearance after penetrating traumatic brain injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fan-Wei Meng ◽  
Jun-Tao Yu ◽  
Jin-Yuan Chen ◽  
Peng-Fei Yang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Tissue Repair ◽  
Cell Formation ◽  
Post Injury ◽  
Cd34 Antigen ◽  
Clearance Mechanism ◽  
Specific Pathogen ◽  
Penetrating Traumatic Brain Injury

AbstractWe characterized the tissue repair response after penetrating traumatic brain injury (pTBI) in this study. Seventy specific pathogen-free Kunming mice were randomly divided into the following groups: normal control, 1, 3, 7, 15, 21, and 30 days after pTBI. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were performed to examine and monitor brain tissue morphology, and the distribution and expression of lymphatic-specific markers lymphatic vessel endothelial receptor-1 (LYVE-1), hematopoietic precursor cluster of differentiation 34 (CD34) antigen, and Prospero-related homeobox-1 (PROX1) protein. H&E staining revealed that damaged and necrotic tissues observed on day 1 at and around the injury site disappeared on day 7, and there was gradual shrinkage and disappearance of the lesion on day 30, suggesting a clearance mechanism. We explored the possibility of lymphangiogenesis causing this clearance as part of the post-injury response. Notably, expression of lymphangiogenesis markers LYVE-1, CD34, and PROX1 was detected in damaged mouse brain tissue but not in normal tissue. Moreover, new lymphatic cells and colocalization of LYVE-1/CD34 and LYVE-1/PROX1 were also observed. Our findings of the formation of new lymphatic cells following pTBI provide preliminary insights into a post-injury clearance mechanism in the brain. Although we showed that lymphatic cells are implicated in brain tissue repair, further research is required to clarify the origin of these cells.

scholarly journals Hypobaria-Induced Oxidative Stress Facilitates Homocysteine Transsulfuration and Promotes Glutathione Oxidation in Rats with Mild Traumatic Brain Injury

2021 ◽  
Vol 13 ◽  
pp. 117957352098819
Author(s):  
Flaubert Tchantchou ◽  
Catriona Miller ◽  
Molly Goodfellow ◽  
Adam Puche ◽  
Gary Fiskum
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glutathione Metabolism ◽  
Compensatory Mechanism ◽  
Oxidative Stress Markers ◽  
Sprague Dawley ◽  
Post Injury ◽  
Stress Markers ◽  
Glutathione Oxidation

Background: United States service members injured in combat theatre are often aeromedically evacuated within a few days to regional military hospitals. Animal and epidemiological research indicates that early exposure to flight hypobaria may worsen brain and other injuries. The mechanisms by which secondary exposure to hypobaria worsen trauma outcomes are not well elucidated. This study tested the hypothesis that hypobaria-induced oxidative stress and associated changes in homocysteine levels play a role in traumatic brain injury (TBI) pathological progression caused by hypobaria. Methods: Male Sprague Dawley rats were exposed to a 6 h hypobaria 24 h after mild TBI by the controlled cortical impact. Plasma and brain tissues were assessed for homocysteine levels, oxidative stress markers or glutathione metabolism, and behavioral deficits post-injury in the absence and presence of hypobaria exposure. Results: We found that hypobaria after TBI increased oxidative stress markers, altered homocysteine metabolism, and promoted glutathione oxidation. Increased glutathione metabolism was driven by differential upregulation of glutathione metabolizing genes. These changes correlated with increased anxiety-like behavior. Conclusion: These data provide evidence that hypobaria exposure after TBI increases oxidative stress and alters homocysteine elimination likely through enhanced glutathione metabolism. This pathway may represent a compensatory mechanism to attenuate free radical formation. Thus, hypobaria-induced enhancement of glutathione metabolism represents a potential therapeutic target for TBI management.

scholarly journals Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice

2021 ◽  
Vol 22 (2) ◽  
pp. 907
Author(s):  
Saef Izzy ◽  
Alexander Brown-Whalen ◽  
Taha Yahya ◽  
Aliyah Sarro-Schwartz ◽  
Gina Jin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Outcomes ◽  
Closed Head Injury ◽  
Tau Pathology ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Tau Mutation ◽  
Injury Causes

Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI.

scholarly journals Antioxidative and Neurotherapeutic Effect of Ascorbic acid on Albino rats Induced with Traumatic Brain Injury

2020 ◽  
Vol 12 (1) ◽  
pp. 922-936
Author(s):  
Ibrahim BULAMA ◽  
Nasiru SULEİMAN ◽  
Lawal BİLBİS ◽  
Abdullahi ABBAS ◽  
Nasiru JİNJİRİ ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Ascorbic Acid ◽  
Brain Injury ◽  
Albino Rats

scholarly journals Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury

2019 ◽  
Vol 20 (3) ◽  
pp. 502 ◽  
Author(s):  
Buyandelger Batsaikhan ◽  
Jing-Ya Wang ◽  
Michael Scerba ◽  
David Tweedie ◽  
Nigel Greig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Neuronal Degeneration ◽  
Neurological Deficits ◽  
Post Injury ◽  
Neuroprotective Effects ◽  
Tnf Α

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.

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