Hemorrhage Associated Mechanisms of Neuroinflammation in Experimental Traumatic Brain Injury

Ma, Xiaotang; Cheng, Yiming; García, Ricardo Juan Bosch; Haorah, James

doi:10.1007/s11481-019-09882-x

Cited by 16 publications

(16 citation statements)

References 68 publications

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“…After alcohol feeding, traumatic brain injury was performed using a uid percussion injury (FPI) model (Amscien Instruments, Richmond, VA) according to our previously described procedure [12,30,31]. Brie y, rats were anesthetized with ketamine (100 mg/kg body weight) and xylazine (10 mg/kg body weight) through intraperitoneal injection and positioned on a stereotaxis frame.…”

Section: Fluid Percussion Injurymentioning

confidence: 99%

“…Since RBCs contain much of the iron found in the body, a possible reason for unresolved, persistent cognitive functional de cits may be neurotoxicity caused by iron overload [11]. We have observed massive RBC aggregations at the site of hemorrhage in our rat model of blunt TBI [12]. This TBI model uses lateral uid percussion injury (FPI) delivered at a moderate pressure to reproduce TBI without skull fracturing to generate hemorrhage, subdural hematoma, and edema.…”

Section: Introductionmentioning

confidence: 97%

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Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Agas

Ravula

et al. 2021

Preprint

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Hemorrhage is often a major component of traumatic brain injury (TBI). Red blood cells (RBCs) accumulated at the hemorrhagic site undergo hemolysis upon energy depletion. Hemolysis of RBCs is expected to release free iron into the central nervous system (CNS) that must be managed to prevent iron neurotoxicity. Here, we examine the hypothesis that chronic alcohol consumption, as a secondary stressor, may increase iron toxicity in an animal model of TBI by altering the iron management pathways. To our best knowledge, this innovative idea with significant scientific premises has not been examined to date. We found huge accumulation of free irons at the site of hemorrhage with evidence of hemolytic activity. Our observation showed that alcohol use altered the three distinct iron management pathways of transferrin/hemosiderin binding, lipocalin 2/heme oxygenase 1/ferritin system, and microglial phagocytosis. Presence of alcohol prolonged the expression of lipocalin 2 at the site of hemorrhage compared with injury alone, while the combined effects of alcohol and TBI elevated the levels of heme oxygenase 1 earlier than TBI alone. Hippocampus, neocortex, and around vessels near the site of impact appeared to be the prominent brain regions of induction. The presence of alcohol notably increased the levels of ferritin that sustained for up to 7 days. We also provide evidence that microglia also play a role in iron management through RBC phagocytosis. These results reveal the intricacy and plasticity of iron management and highlight the importance of proper iron regulation in the CNS.

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Section: Fluid Percussion Injurymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Agas

Ravula

et al. 2021

Preprint

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“…Hemorrhage [1], [2] is a medical term referring to bleeding within or out of the body. Internal bleeding of the brain is known as Brain Hemorrhage [3].…”

Section: Introductionmentioning

confidence: 99%

“…This is caused by a sudden blood clot [4] in arteries that supply blood to the brain or internal bleeding in the surrounding tissues of the brain due to rupturing of the arteries [5]- [8]. The brain cells got damage by this bleeding and the most common causes [9] are trauma [1], high blood pressure [10], aneurysm, blood vessel abnormalities [11], amyloid angiopathy, bleeding disorders and brain tumors [12], [13]. Those are the major causes of death and severe disability.…”

Section: Introductionmentioning

confidence: 99%

BHCNet: Neural Network-Based Brain Hemorrhage Classification Using Head CT Scan

et al. 2021

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Brain Hemorrhage is the eruption of the brain arteries due to high blood pressure or blood clotting that could be a cause of traumatic injury or death. It is the medical emergency in which a doctor also need years of experience to immediately diagnose the region of the internal bleeding before starting the treatment. In this study, the deep learning models Convolutional Neural Network (CNN), hybrid models CNN+LSTM and CNN+GRU are proposed for the Brain Hemorrhage classification. The 200 head CT scan images dataset is used to boost the accuracy rate and computational power of the deep learning models. The major aim of this study is to use the abstraction power of deep learning on a set of fewer images because in most crucial cases extensive datasets are not available on the spot. The image augmentation and imbalancing the dataset methods are adopted with CNN model to design a unique architecture and named as Brain Hemorrhage Classification based on Neural Network (BHCNet). The performance of the proposed approach are analyzed in terms of accuracy, precision, sensitivity, specificity and F1-score. Further, the experimental results are evaluated by comparative analyses of the balanced and imbalanced dataset with CNN, CNN+LSTM and CNN+GRU models. The promising results are achieved with CNN by imbalancing the dataset and gain highest accuracy that outperforms the hybrid CNN+LSTM and CNN+GRU models. The results reveals the effectiveness of the proposed model for accurate prediction to save the life of the patient in the meantime and fast employment in the real life scenario.

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“…In a prospective clinical study, it was shown that patients who required transfusions in the context of a trauma due to hemorrhage had a significantly increased risk of developing MOF [6]: 30% of the patients with systolic hypotension (<90 mmHg), metabolic acidosis (base excess −6 mmol/L), and/or requiring red blood cell transfusion within the first 12 h developed MOF within 2-3 days [6]. The underlying pathophysiological mechanism is systemic [2,3] and, in TBI, also local hyper-(neuro-)inflammation [7,8], which originates, in addition to direct mechanical/physical trauma, from tissue hypoxia due to blood loss and reduced perfusion [9]. TBI significantly worsens the acute prognosis of patients with polytrauma: for example, a retrospective longterm analysis over 15 years showed that TBI was responsible for 58%, whereas hemorrhagic shock (HS) was responsible for 28% of deaths after major trauma [10].…”

Section: Introduction Polytrauma-hemorrhage and Brain Injurymentioning

confidence: 99%

Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide

Merz

McCook

Denoix

et al. 2021

IJMS

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This paper explored the potential mediating role of hydrogen sulfide (H2S) and the oxytocin (OT) systems in hemorrhagic shock (HS) and/or traumatic brain injury (TBI). Morbidity and mortality after trauma mainly depend on the presence of HS and/or TBI. Rapid “repayment of the O2 debt” and prevention of brain tissue hypoxia are cornerstones of the management of both HS and TBI. Restoring tissue perfusion, however, generates an ischemia/reperfusion (I/R) injury due to the formation of reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, pre-existing-medical-conditions (PEMC’s) can aggravate the occurrence and severity of complications after trauma. In addition to the “classic” chronic diseases (of cardiovascular or metabolic origin), there is growing awareness of psychological PEMC’s, e.g., early life stress (ELS) increases the predisposition to develop post-traumatic-stress-disorder (PTSD) and trauma patients with TBI show a significantly higher incidence of PTSD than patients without TBI. In fact, ELS is known to contribute to the developmental origins of cardiovascular disease. The neurotransmitter H2S is not only essential for the neuroendocrine stress response, but is also a promising therapeutic target in the prevention of chronic diseases induced by ELS. The neuroendocrine hormone OT has fundamental importance for brain development and social behavior, and, thus, is implicated in resilience or vulnerability to traumatic events. OT and H2S have been shown to interact in physical and psychological trauma and could, thus, be therapeutic targets to mitigate the acute post-traumatic effects of chronic PEMC’s. OT and H2S both share anti-inflammatory, anti-oxidant, and vasoactive properties; through the reperfusion injury salvage kinase (RISK) pathway, where their signaling mechanisms converge, they act via the regulation of nitric oxide (NO).

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Hemorrhage Associated Mechanisms of Neuroinflammation in Experimental Traumatic Brain Injury

Cited by 16 publications

References 68 publications

Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

BHCNet: Neural Network-Based Brain Hemorrhage Classification Using Head CT Scan

Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide

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