scholarly journals Phenelzine Mitochondrial Functional Preservation and Neuroprotection after Traumatic Brain Injury Related to Scavenging of the Lipid Peroxidation-Derived Aldehyde 4-Hydroxy-2-Nonenal

2013 ◽  
Vol 33 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Indrapal N Singh ◽  
Lesley K Gilmer ◽  
Darren M Miller ◽  
John E Cebak ◽  
Juan A Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Lipid Peroxidation ◽  
Brain Injury ◽  
Neuroprotective Effect ◽  
Respiratory Control ◽  
Dependent Manner ◽  
Cortical Tissue ◽  
Concentration Dependent Manner ◽  
Respiratory Dysfunction ◽  
Tissue Sparing

Phenelzine (PZ) is a scavenger of the lipid peroxidation (LP)-derived reactive aldehyde 4-hydroxynonenal (4-HNE) due to its hydrazine functional group, which can covalently react with 4-HNE. In this study, we first examined the ability of PZ to prevent the respiratory depressant effects of 4-HNE on normal isolated brain cortical mitochondria. Second, in rats subjected to controlled cortical impact traumatic brain injury (CCI-TBI), we evaluated PZ (10 mg/kg subcutaneously at 15 minutes after CCI-TBI) to attenuate 3-hour post-TBI mitochondrial respiratory dysfunction, and in separate animals, to improve cortical tissue sparing at 14 days. While 4-HNE exposure inhibited mitochondrial complex I and II respiration in a concentration-dependent manner, pretreatment with equimolar concentrations of PZ antagonized these effects. Western blot analysis demonstrated a PZ decrease in 4-HNE in mitochondrial proteins. Mitochondria isolated from peri-contusional brain tissue of CCI-TBI rats treated with vehicle at 15 minutes after injury showed a 37% decrease in the respiratory control ratio (RCR) relative to noninjured mitochondria. In PZ-treated rats, RCR suppression was prevented ( P < 0.05 versus vehicle). In another cohort, PZ administration increased spared cortical tissue from 86% to 97% ( P < 0.03). These results suggest that PZ's neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE.

scholarly journals Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation

Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 47-53 ◽  
Author(s):  
Wenyong Pan ◽  
Zhigang Cao ◽  
Dongyang Liu ◽  
Yingbin Jiao
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protective Effect ◽  
Neuronal Degeneration ◽  
Neuroprotective Effect ◽  
B Cell Lymphoma ◽  
Treated Group ◽  
Dependent Manner ◽  
And Oxidative Stress

Background: Traumatic brain injury (TBI) is considered a major burden across the globe affecting both individuals and their families. Therefore, the present study was conducted to determine the protective effect of diphenhydramine (DPM) against TBI in experimental rats. Methods: The effect of DPM was evaluated on the cerebral edema (CE) and neuronal degeneration after the induction of experimental brain injury in rats. The effect of DPM was also investigated on the inflammatory cytokines, for example, tumor necrosis factor-α and interleukin 1β and oxidative stress markers, such as malondialdehyde, superoxide dismutase, and glutathione peroxidase. Western blot analysis was used to investigate the effect of DPM on B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3. Results: Results of the study suggest that DPM causes reduction in CE and prevents neuronal degeneration. It also causes reduction in inflammation and oxidative stress in a dose-dependent manner. The level of Bax was found to be elevated, together with reduction in the Bcl-2 level in the DPM-treated group. Conclusion: DPM exerts a neuroprotective effect after TBI via the attenuation of oxidative stress, inflammation, and mitochondrial apoptosis pathways.

scholarly journals Peroxynitrite-Mediated Protein Nitration and Lipid Peroxidation in a Mouse Model of Traumatic Brain Injury

2004 ◽  
Vol 21 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Edward D. Hall ◽  
Megan R. Detloff ◽  
Kjell Johnson ◽  
Nancy C. Kupina
Keyword(s):  
Traumatic Brain Injury ◽  
Lipid Peroxidation ◽  
Brain Injury ◽  
Mouse Model ◽  
Protein Nitration

scholarly journals Moderate and severe traumatic brain injury: effect of blood alcohol concentration on Glasgow Coma Scale score and relation to computed tomography findings

2015 ◽  
Vol 122 (1) ◽  
pp. 211-218 ◽  
Author(s):  
Nils Petter Rundhaug ◽  
Kent Gøran Moen ◽  
Toril Skandsen ◽  
Kari Schirmer-Mikalsen ◽  
Stine B. Lund ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Injury Severity ◽  
Blood Alcohol Concentration ◽  
Alcohol Concentration ◽  
Dependent Manner ◽  
Blood Alcohol ◽  
Severe Tbi ◽  
Gcs Score ◽  
Dose Dependent

OBJECT The influence of alcohol is assumed to reduce consciousness in patients with traumatic brain injury (TBI), but research findings are divergent. The aim of this investigation was to study the effects of different levels of blood alcohol concentration (BAC) on the Glasgow Coma Scale (GCS) scores in patients with moderate and severe TBI and to relate the findings to brain injury severity based on the admission CT scan. METHODS In this cohort study, 265 patients (age range 16–70 years) who were admitted to St. Olavs University Hospital with moderate and severe TBI during a 7-year period were prospectively registered. Of these, 217 patients (82%) had measured BAC. Effects of 4 BAC groups on GCS score were examined with ordinal logistic regression analyses, and the GCS scores were inverted to give an OR > 1. The Rotterdam CT score based on admission CT scan was used to adjust for brain injury severity (best score 1 and worst score 6) by stratifying patients into 2 brain injury severity groups (Rotterdam CT scores of 1–3 and 4–6). RESULTS Of all patients with measured BAC, 91% had intracranial CT findings and 43% had BAC > 0 mg/dl. The median GCS score was lower in the alcohol-positive patients (6.5, interquartile range [IQR] 4–10) than in the alcohol-negative patients (9, IQR 6–13; p < 0.01). No significant differences were found between alcohol-positive and alcohol-negative patients regarding other injury severity variables. Increasing BAC was a significant predictor of lower GCS score in a dose-dependent manner in age-adjusted analyses, with OR 2.7 (range 1.4–5.0) and 3.2 (range 1.5–6.9) for the 2 highest BAC groups (p < 0.01). Subgroup analyses showed an increasing effect of BAC group on GCS scores in patients with Rotterdam CT scores of 1–3: OR 3.1 (range 1.4–6.6) and 6.7 (range 2.7–16.7) for the 2 highest BAC groups (p < 0.01). No such relationship was found in patients with Rotterdam CT scores of 4–6 (p = 0.14–0.75). CONCLUSIONS Influence of alcohol significantly reduced the GCS score in a dose-dependent manner in patients with moderate and severe TBI and with Rotterdam CT scores of 1–3. In patients with Rotterdam CT scores of 4–6, and therefore more CT findings indicating increased intracranial pressure, the brain injury itself seemed to overrun the depressing effect of the alcohol on the CNS. This finding is in agreement with the assumption of many clinicians in the emergency situation.

The Neuroprotective Effect of Salubrinal in a Mouse Model of Traumatic Brain Injury

2015 ◽  
Vol 17 (1) ◽  
pp. 58-70 ◽  
Author(s):  
Vardit Rubovitch ◽  
Shani Barak ◽  
Lital Rachmany ◽  
Renana Baratz Goldstein ◽  
Yael Zilberstein ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Neuroprotective Effect

scholarly journals Regulatory T cells exhibit neuroprotective effect in a mouse model of traumatic brain injury

2016 ◽  
Vol 14 (6) ◽  
pp. 5556-5566 ◽  
Author(s):  
Yunhu Yu ◽  
Fang Cao ◽  
Qishan Ran ◽  
Xiaochuan Sun
Keyword(s):  
Traumatic Brain Injury ◽  
T Cells ◽  
Brain Injury ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Neuroprotective Effect

scholarly journals Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 943 ◽  
Author(s):  
Helene Ismail ◽  
Zaynab Shakkour ◽  
Maha Tabet ◽  
Samar Abdelhady ◽  
Abir Kobaisi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Free Radical Scavenger ◽  
Health Concern ◽  
Radical Scavenger ◽  
History Of ◽  
Ionic Imbalance

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

scholarly journals Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time-Dependent Manner

Shock ◽  
2019 ◽  
Vol 52 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Susannah E. Nicholson ◽  
Lora T. Watts ◽  
David M. Burmeister ◽  
Daniel Merrill ◽  
Shannon Scroggins ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Time Dependent ◽  
Dependent Manner ◽  
Gastrointestinal Microbiome ◽  
Moderate Traumatic Brain Injury
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