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

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.

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Mild traumatic brain injury affects the features of migraine

The Journal of Headache and Pain ◽

10.1186/s10194-021-01291-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ryotaro Ishii ◽

Todd J. Schwedt ◽

Meesha Trivedi ◽

Gina Dumkrieger ◽

Melissa M. Cortez ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Physical Abuse ◽

Mild Traumatic Brain Injury ◽

Clinical Course ◽

Categorical Variables ◽

Continuous Variables ◽

Lack Of Sleep ◽

History Of ◽

The Impact

Abstract Background Headache is one of the most common symptoms after concussion, and mild traumatic brain injury (mTBI) is a risk factor for chronic migraine (CM). However, there remains a paucity of data regarding the impact of mTBI on migraine-related symptoms and clinical course. Methods Of 2161 migraine patients who participated in the American Registry for Migraine Research between February 2016 and March 2020, 1098 completed questions assessing history of TBI (50.8%). Forty-four patients reported a history of moderate to severe TBI, 413 patients reported a history of mTBI. Patients’ demographics, headache symptoms and triggers, history of physical abuse, allodynia symptoms (ASC-12), migraine disability (MIDAS), depression (PHQ-2), and anxiety (GAD-7) were compared between migraine groups with (n = 413) and without (n = 641) a history of mTBI. Either the chi-square-test or Fisher’s exact test, as appropriate, was used for the analyses of categorical variables. The Mann-Whitney test was used for the analyses of continuous variables. Logistic regression models were used to compare variables of interest while adjusting for age, gender, and CM. Results A significantly higher proportion of patients with mTBI had CM (74.3% [307/413] vs. 65.8% [422/641], P = 0.004), had never been married or were divorced (36.6% [147/402] vs. 29.4% [187/636], P = 0.007), self-reported a history of physical abuse (24.3% [84/345] vs. 14.3% [70/491], P < 0.001), had mild to severe anxiety (50.5% [205/406] vs. 41.0% [258/630], P = 0.003), had headache-related vertigo (23.0% [95/413] vs. 15.9% [102/640], P = 0.009), and difficulty finding words (43.0% [174/405] vs. 32.9% [208/633], P < 0.001) in more than half their attacks, and headaches triggered by lack of sleep (39.4% [155/393] vs. 32.6% [198/607], P = 0.018) and reading (6.6% [26/393] vs. 3.0% [18/607], P = 0.016), compared to patients without mTBI. Patients with mTBI had significantly greater ASC-12 scores (median [interquartile range]; 5 [1–9] vs. 4 [1–7], P < 0.001), MIDAS scores (42 [18–85] vs. 34.5 [15–72], P = 0.034), and PHQ-2 scores (1 [0–2] vs. 1 [0–2], P = 0.012). Conclusion Patients with a history of mTBI are more likely to have a self-reported a history of physical abuse, vertigo, and allodynia during headache attacks, headaches triggered by lack of sleep and reading, greater headache burden and headache disability, and symptoms of anxiety and depression. This study suggests that a history of mTBI is associated with the phenotype, burden, clinical course, and associated comorbid diseases in patients with migraine, and highlights the importance of inquiring about a lifetime history of mTBI in patients being evaluated for migraine.

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Traumatic Brain Injury: The Silent Epidemic

AACN Advanced Critical Care ◽

10.4037/15597768-1992-1002 ◽

1992 ◽

Vol 3 (1) ◽

pp. 9-18 ◽

Cited By ~ 7

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

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Improving the translational potential of rodent models to study the behavioral and pathophysiological effects of repetitive mild traumatic brain injury

Journal of Neurophysiology ◽

10.1152/jn.00898.2017 ◽

2018 ◽

Vol 120 (1) ◽

pp. 1-3

Author(s):

Megan E. Huibregtse

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Outcome Measures ◽

Mild Traumatic Brain Injury ◽

Chronic Traumatic Encephalopathy ◽

Rodent Models ◽

Head Impacts ◽

Repetitive Head Impacts ◽

The Impact

Chronic traumatic encephalopathy (CTE) is thought to be caused by repetitive head impacts. Consequently, there is a need to develop rodent models to better understand the behavioral and pathophysiological changes of repetitive mild traumatic brain injury (rmTBI) and to determine the link between rmTBI and CTE. This Neuro Forum article reviews recent rodent rmTBI models, comparing the impact methods and outcome measures in terms of translational potential.

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Apoptotic and Antiapoptotic Mechanisms after Traumatic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200110000-00007 ◽

2001 ◽

Vol 21 (10) ◽

pp. 1189-1198 ◽

Cited By ~ 120

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.

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

Antioxidants ◽

10.3390/antiox10060898 ◽

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.

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

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80136 ◽

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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The Immune System's Role in the Consequences of Mild Traumatic Brain Injury (Concussion)

Frontiers in Immunology ◽

10.3389/fimmu.2021.620698 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura N. Verboon ◽

Hiren C. Patel ◽

Andrew D. Greenhalgh

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Immune Cell ◽

Chronic Traumatic Encephalopathy ◽

Anxiety And Depression ◽

Mild Tbi ◽

Patient Health ◽

History Of ◽

The Impact

Mild traumatic brain injury (mild TBI), often referred to as concussion, is the most common form of TBI and affects millions of people each year. A history of mild TBI increases the risk of developing emotional and neurocognitive disorders later in life that can impact on day to day living. These include anxiety and depression, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD). Actions of brain resident or peripherally recruited immune cells are proposed to be key regulators across these diseases and mood disorders. Here, we will assess the impact of mild TBI on brain and patient health, and evaluate the recent evidence for immune cell involvement in its pathogenesis.

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Prion-Like Propagation Mechanisms in Tauopathies and Traumatic Brain Injury: Challenges and Prospects

Biomolecules ◽

10.3390/biom10111487 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1487

Author(s):

Hadeel Alyenbaawi ◽

W. Ted Allison ◽

Sue-Ann Mok

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Chronic Traumatic Encephalopathy ◽

Tissue Level ◽

Therapeutic Approaches ◽

Tau Pathology ◽

The Brain

The accumulation of tau protein in the form of filamentous aggregates is a hallmark of many neurodegenerative diseases such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). These dementias share traumatic brain injury (TBI) as a prominent risk factor. Tau aggregates can transfer between cells and tissues in a “prion-like” manner, where they initiate the templated misfolding of normal tau molecules. This enables the spread of tau pathology to distinct parts of the brain. The evidence that tauopathies spread via prion-like mechanisms is considerable, but work detailing the mechanisms of spread has mostly used in vitro platforms that cannot fully reveal the tissue-level vectors or etiology of progression. We review these issues and then briefly use TBI and CTE as a case study to illustrate aspects of tauopathy that warrant further attention in vivo. These include seizures and sleep/wake disturbances, emphasizing the urgent need for improved animal models. Dissecting these mechanisms of tauopathy progression continues to provide fresh inspiration for the design of diagnostic and therapeutic approaches.

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