Time-dependent hemeoxygenase-1, lipocalin-2 and ferritin induction after non-contusion traumatic brain injury

Russell, Nicholas H.; Black, Richard J.; Lee, Nancy N.; Doperalski, Adele E.; Reeves, Thomas M.; Phillips, Linda R.

doi:10.1016/j.brainres.2019.146466

Cited by 15 publications

(15 citation statements)

References 99 publications

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“…1, Turnbull's Blue panel at 2 hours). This explanation is in agreement with the ndings of others [22]. Free iron, whether as a ferrous cation or an unbound ferric species, is readily absorbed by cells and can be very toxic [36].…”

Section: Hemosiderin and Transferrin Bindingsupporting

confidence: 92%

“…al. (2019) that also looked at the expression levels of LCN2, HO-1, and F-LC in an FPI model of TBI [22].…”

Section: Moderate Lateral Uid Percussion Injurymentioning

confidence: 99%

“…The hemolytic product iron is managed by several different proteins to prevent possible iron toxicity that may develop from iron accumulation. Chief iron regulators include heme oxygenase-1 (HO-1, iron release), lipocalin 2 (LCN2, intracellular iron transport), ferritin light chain (F-LC, iron storage), transferrin (extracellular iron transport), and hemosiderin (iron storage and sequestration) [21,22]. Together, these proteins combine to form two distinct pathways for iron management, the LCN2/HO-1/F-LC system for intracellular iron and transferrin/hemosiderin binding for extracellular iron.…”

Section: Introductionmentioning

confidence: 99%

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Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Agas

Ravula

et al. 2022

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) which 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 a rat model of TBI by altering the iron management pathways. We found large accumulations of free iron at the site of hemorrhage with evidence of hemolytic activity. Our observations demonstrate that alcohol use can alter the three distinct iron management pathways: transferrin/hemosiderin binding, lipocalin 2/heme oxygenase 1/ferritin system, and possible microglial phagocytosis. Presence of alcohol prolonged the expression of lipocalin 2 as well as increased and sustained levels of ferritin, while the combined effects of alcohol and TBI elevated the levels of heme oxygenase 1 faster than TBI alone. The hippocampus, neocortex, ventricles, and around vessels near the site of impact appeared to be the prominent brain regions of induction. In addition, we provide evidence that microglia my also play a role in iron management through RBC phagocytosis.

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Section: Hemosiderin and Transferrin Bindingsupporting

confidence: 92%

“…al. (2019) that also looked at the expression levels of LCN2, HO-1, and F-LC in an FPI model of TBI [22].…”

Section: Moderate Lateral Uid Percussion Injurymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Agas

Ravula

et al. 2022

Preprint

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“…Interpretation of ferritin is more challenging. Ferritin as an iron binding protein is ubiquitously expressed; both mechanistically and as a CSF marker ferritin has been related to various CNS disorders and conditions, including traumatic brain injury, and might in the end constitute a sensitive, but not very specific marker of a range of CNS pathologies (Finazzi & Arosio, 2014; Kolodziej et al, 2014; Ondruschka et al, 2018; Russell et al., 2019). Under pathological conditions, extracellular ferritin could be derived from different cellular sources.…”

Section: Discussionmentioning

confidence: 99%

Interrelations of Alzheimer´s disease candidate biomarkers neurogranin, fatty acid‐binding protein 3 and ferritin to neurodegeneration and neuroinflammation

Brosseron

Kleemann

Kolbe

et al. 2020

Journal of Neurochemistry

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There is growing evidence that promising biomarkers of inflammation in Alzheimer´s disease (AD) and other neurodegenerative diseases correlate strongest to levels of tau or neurofilament, indicating an inflammatory response to neuronal damage or death. To test this hypothesis, we investigated three AD candidate markers (ferritin, fatty acid binding protein 3 (FABP‐3), and neurogranin) in interrelation to established AD and inflammatory protein markers. We further aimed to determine if such interrelations would be evident in pathological subjects only or also under non‐pathological circumstances. Cerebrospinal fluid levels of the three proteins were quantified in samples from the University Clinic of Bonn (UKB) Department of Neurodegenerative Diseases & Geriatric Psychiatry, Germany. Data were analyzed based on clinical or biomarker‐defined stratification of subjects with adjustment for covariates age, sex, and APOE status. Levels of ferritin, FABP‐3 and neurogranin were elevated in subjects with pathological levels of t‐tau independent of beta‐amyloid status. The three markers correlated with each other, tau isoforms, age, and those inflammatory markers previously described as related to neurodegeneration, predominantly sTREM2, macrophage migration inhibitory factor, soluble vascular endothelial growth factor receptor, soluble vascular cell adhesion molecule 1 (sVCAM‐1), and C1q. These interrelations existed in subjects with pathological and sub‐pathological tau levels, in particular for FABP‐3 and neurogranin. Relations to ferritin were independent of absolute levels of tau, too, but showed differing trajectories between pathological and non‐pathological subjects. A specific set of inflammatory markers is highly related to markers of neuronal damage such as tau, neurogranin, or FABP‐3. These proteins could be used as readouts of the inflammatory response during the neurodegeneration phase of AD.

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“…Following TBI, dysregulation of endocrine signalling cascades have been reported for various axes including insulin [ 160 ], pituitary dysfunction [ 161 ] with disruptions in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis [ 162 ], antidiuretic hormone (ADH, vasopressin) [ 163 ], the hypothalamic-pituitary-adrenal (HPA) axis [ 164 ], sexual hormones [ 164 , 165 ], thyroid-stimulating hormone (TSH) [ 166 , 167 ], alterations in leptin signalling [ 75 , 168 ], osteocalcin (OCN) [ 168 ] and lipocalin 2 [ 169 , 170 ]. Further analysis depicted a bidirectional interaction between the brain and the endocrine system in TBI [ 171 , 172 ].…”

Section: Interaction Of Tsci and Tbimentioning

confidence: 99%

Future Perspectives in Spinal Cord Repair: Brain as Saviour? TSCI with Concurrent TBI: Pathophysiological Interaction and Impact on MSC Treatment

Köhli

Otto

Jahn

et al. 2021

Cells

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Traumatic spinal cord injury (TSCI), commonly caused by high energy trauma in young active patients, is frequently accompanied by traumatic brain injury (TBI). Although combined trauma results in inferior clinical outcomes and a higher mortality rate, the understanding of the pathophysiological interaction of co-occurring TSCI and TBI remains limited. This review provides a detailed overview of the local and systemic alterations due to TSCI and TBI, which severely affect the autonomic and sensory nervous system, immune response, the blood–brain and spinal cord barrier, local perfusion, endocrine homeostasis, posttraumatic metabolism, and circadian rhythm. Because currently developed mesenchymal stem cell (MSC)-based therapeutic strategies for TSCI provide only mild benefit, this review raises awareness of the impact of TSCI–TBI interaction on TSCI pathophysiology and MSC treatment. Therefore, we propose that unravelling the underlying pathophysiology of TSCI with concomitant TBI will reveal promising pharmacological targets and therapeutic strategies for regenerative therapies, further improving MSC therapy.

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Time-dependent hemeoxygenase-1, lipocalin-2 and ferritin induction after non-contusion traumatic brain injury

Cited by 15 publications

References 99 publications

Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Interrelations of Alzheimer´s disease candidate biomarkers neurogranin, fatty acid‐binding protein 3 and ferritin to neurodegeneration and neuroinflammation

Future Perspectives in Spinal Cord Repair: Brain as Saviour? TSCI with Concurrent TBI: Pathophysiological Interaction and Impact on MSC Treatment

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