Serial quantitative neuroimaging of iron in the intracerebral hemorrhage pig model

Iron released after intracerebral hemorrhage (ICH) is damaging to the brain. Measurement of the content and distribution of iron in the hematoma could predict brain damage. In this study, 16 Yorkshire piglets were subjected to autologous blood injection ICH model and studied longitudinally using quantitative susceptibility mapping and R2* relaxivity MRI on day 1 and 7 post-ICH. Phantom calibration of susceptibility demonstrated (1) iron distribution heterogeneity within the hematoma and (2) natural absorption of iron from 154 ± 78 µg/mL (day 1) to 127 ± 33 µg/mL (day 7). R2* in the hematoma decreased at day 7. This method could be adopted for ICH in humans.

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Abstract TP348: Quantitative Serial Neuroimaging of Iron in the Intracerebral Hemorrhage Pig Model

Stroke ◽

10.1161/str.48.suppl_1.tp348 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Muhammad E Haque ◽

Refaat E Gabr ◽

Xiurong Zhao ◽

Khader M Hasan ◽

Ponnada A Narayana ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Autologous Blood ◽

Iron Concentration ◽

Susceptibility Mapping ◽

Pig Model ◽

Large Animal ◽

Quantitative Susceptibility Mapping ◽

Secondary Damage ◽

Susceptibility Maps ◽

The Brain

Objective: To serially quantify changes of iron concentration within hematomas in the intracerebral hemorrhage (ICH) pig model using non-invasive R2* and quantitative susceptibility mapping (QSM) MRI methods. Introduction: Hemolysis-related release of hemoglobin/heme/free iron after ICH causes cytotoxic injury. An accurate post hemorrhage assessment of iron would be valuable to develop strategies to prevent secondary damage. The T2* relaxation rate (R2* =1/T2*) on MRI depends on the regional oxy- versus deoxyhemoglobin. Post-ICH excess of deoxyhemoglobin has been applied as a quantitative marker to estimate iron in the brain. However, quantitative susceptibility mapping (QSM) is a new MRI technique that can quantify iron concentration within the hematoma by measuring induced magnetic susceptibility. Using R2* mapping and QSM in a large animal ICH model, we measured spatiotemporal changes in iron concentration in the brain. Methods: Lobar ICH was induced by infusion of 2.5 ml autologous blood in 8 Yorkshire pigs with average age/wt of 4-6wk/12.5±2.5kg. MRI was obtained at days 1 and 7. A 3D anatomical and multi-echo gradient echo images were obtained on a clinical 3.0 T Philips Ingenia MRI system. Parametric R2* and susceptibility maps were generated. Regions of interest were placed within hematoma and contralesional CSF. Results: R2* measurements in the hematoma at day 1 and day 7 were 41.3 ± 7.3 and 37.7 ± 7.7 s -1 , respectively, whereas the corresponding susceptibility measurements were 0.75± 0.3 and 0.70 ± 0.5 ppm. The CSF R2* were 5.53 ± 2.1 and 6.85 ± 2.4 s -1 , whereas susceptibility showed 0.06 ± 0.16 and 0.02 ± 0.03 ppm at the two time points. Both R2* and QSM showed no significant change in iron concentration within the hematoma ROI with p-value of 0.18 and 0.72 over a week. Absence of hyperintense regions remote from the hematoma in susceptibility maps suggested lack of diffuse iron deposition. Good correlation was observed between R2* and QSM (correlation coefficient 0.83 and 0.78 within hematoma, and -0.66 and -0.07 within CSF, at day 1 and 7, respectively). Conclusion: R2* and especially QSM, with their ability to provide quantitative iron content, are valuable tools to test new ICH treatments particularly targeting iron in this large animal model.

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Autologous Blood Injection to Model Spontaneous Intracerebral Hemorrhage in Mice

Journal of Visualized Experiments ◽

10.3791/2618 ◽

2011 ◽

Cited By ~ 5

Author(s):

Lauren H. Sansing ◽

Scott E. Kasner ◽

Louise McCullough ◽

Puneet Agarwal ◽

Frank A. Welsh ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Autologous Blood ◽

Spontaneous Intracerebral Hemorrhage ◽

Autologous Blood Injection ◽

Blood Injection

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Divergent Functions of Tissue-Resident and Blood-Derived Macrophages in the Hemorrhagic Brain

Stroke ◽

10.1161/strokeaha.120.032196 ◽

2021 ◽

Vol 52 (5) ◽

pp. 1798-1808

Author(s):

Che-Feng Chang ◽

Brittany A. Goods ◽

Michael H. Askenase ◽

Hannah E. Beatty ◽

Artem Osherov ◽

...

Keyword(s):

Cell Proliferation ◽

T Cell ◽

Autologous Blood ◽

T Cell Proliferation ◽

Autologous Blood Injection ◽

Blood Injection ◽

Antigen Presenting ◽

Proliferation Assays ◽

The Brain

Background and Purpose: Brain tissue-resident microglia and monocyte-derived macrophages (MDMs) are innate immune cells that contribute to the inflammatory response, phagocytosis of debris, and tissue repair after injury. We have previously reported that both microglia and MDMs transition from proinflammatory to reparative phenotypes over days after an intracerebral hemorrhage (ICH). However, their individual functional properties in the brain remain largely unknown. Here we characterized the differences between microglia and MDMs and further elucidate their distinct activation states and functional contributions to the pathophysiology and recovery after ICH. Methods: Autologous blood injection was used to model ICH in mice. Longitudinal transcriptomic analyses on isolated microglia and MDMs from mice at days 1, 3, 7 and 10 after ICH and naive controls identified core transcriptional programs that distinguish these cells. Imaging flow cytometry and in vivo phagocytosis assays were used to study phagocytic ability of microglia and MDMs. Antigen presentation was evaluated by ovalbumin-OTII CD4 T-cell proliferation assays with bone marrow–derived macrophages and primary microglia cultures. Results: MDMs had higher phagocytic activity and higher erythrophagocytosis in the ICH brain. Differential gene expression revealed distinct transcriptional signatures in the MDMs and microglia after ICH. MDMs had higher expression of MHCII (major histocompatibility complex class II) genes than microglia at all time points and greater ability to induce antigen-specific T-cell proliferation. Conclusions: The different ontogeny of microglia and MDMs lead to divergent responses and functions in the inflamed brain as these 2 cell populations differ in phagocytic functions and antigen-presenting capabilities in the brain after ICH.

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Autologous Blood Injection and Wrist Immobilisation for Chronic Lateral Epicondylitis

Advances in Orthopedics ◽

10.1155/2012/387829 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Nicola Massy-Westropp ◽

Stuart Simmonds ◽

Suzanne Caragianis ◽

Andrew Potter

Keyword(s):

Tennis Elbow ◽

Autologous Blood ◽

Lateral Epicondylitis ◽

Contralateral Limb ◽

Cortisone Injection ◽

Autologous Blood Injection ◽

Blood Injection ◽

And Function ◽

Prospective Longitudinal ◽

Extensor Carpi Radialis

Purpose. This study explored the effect of autologous blood injection (with ultrasound guidance) to the elbows of patients who had radiologically assessed degeneration of the origin of extensor carpi radialis brevis and failed cortisone injection/s to the lateral epicondylitis.Methods. This prospective longitudinal series involved preinjection assessment of pain, grip strength, and function, using the patient-rated tennis elbow evaluation. Patients were injected with blood from the contralateral limb and then wore a customised wrist support for five days, after which they commenced a stretching, strengthening, and massage programme with an occupational therapist. These patients were assessed after six months and then finally between 18 months and five years after injection, using the patient-rated tennis elbow evaluation.Results. Thirty-eight of 40 patients completed the study, showing significant improvement in pain; the worst pain decreased by two to five points out of a 10-point visual analogue for pain. Self-perceived function improved by 11–25 points out of 100. Women showed significant increase in grip, but men did not.Conclusions. Autologous blood injection improved pain and function in a worker’s compensation cohort of patients with chronic lateral epicondylitis, who had not had relief with cortisone injection.

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Long-term success with autologous blood injection for leaking trabeculectomy blebs

British Journal of Ophthalmology ◽

10.1136/bjo.2009.164160 ◽

2010 ◽

Vol 94 (3) ◽

pp. 392-393 ◽

Cited By ~ 3

Author(s):

C. Dinah ◽

B. Bhachech ◽

G. Ghosh

Keyword(s):

Autologous Blood ◽

Autologous Blood Injection ◽

Blood Injection

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Blood Injection Intracerebral Hemorrhage Pig Model

Springer Series in Translational Stroke Research - Animal Models of Acute Neurological Injury ◽

10.1007/978-3-030-16082-1_22 ◽

2019 ◽

pp. 303-309

Author(s):

Yuxiang Gu ◽

Shenglong Cao ◽

Guohua Xi ◽

Ya Hua

Keyword(s):

Intracerebral Hemorrhage ◽

Pig Model ◽

Blood Injection

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Intracerebral Injection of Heme Induces Lipid Peroxidation, Neuroinflammation, and Sensorimotor Deficits

Stroke ◽

10.1161/strokeaha.120.031911 ◽

2021 ◽

Author(s):

Luiz Ricardo C. Vasconcellos ◽

Letícia Martimiano ◽

Danillo Pereira Dantas ◽

Filipe Mota Fonseca ◽

Hilton Mata-Santos ◽

...

Keyword(s):

Lipid Peroxidation ◽

Signaling Pathway ◽

Brain Damage ◽

Autologous Blood ◽

Mapk Signaling ◽

Heme Oxygenase 1 ◽

Dependent Manner ◽

In Vivo Models ◽

Sensorimotor Deficits ◽

The Brain

Background and Purpose: Heme is a red blood cell component released in the brain parenchyma following intracerebral hemorrhage. However, the study of the pathophysiological mechanisms triggered by heme in the brain is hampered by the lack of well-established in vivo models of intracerebral heme injection. This study aims to optimize and characterize a protocol of intrastriatal heme injection in mice, with a focus on the induction of lipid peroxidation, neuroinflammation and, ultimately, sensorimotor deficits. We also evaluated the involvement of NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), an inflammasome sensor, in the behavior deficits induced by heme in this model. Methods: Mice were injected with heme in the striatum for the evaluation of neuroinflammation and brain damage through histological and biochemical techniques. Immunoblot was used to evaluate the expression of proteins involved in heme/iron metabolism and antioxidant responses and the activation of the MAPK (mitogen-activated protein kinase) signaling pathway. For the assessment of neurological function, we followed-up heme-injected mice for 2 weeks using the rotarod, elevated body swing, and cylinder tests. Mice injected with the vehicle (sham), or autologous blood were used as controls. Results: Heme induced lipid peroxidation and inflammation in the brain. Moreover, heme increased the expression of HO-1 (heme oxygenase-1), ferritin, p62, and superoxide dismutase 2, and activated the MAPK signaling pathway promoting pro-IL (interleukin)-1β production and its cleavage to the active form. Heme-injected mice exhibited signs of brain damage and reactive astrogliosis around the injection site. Behavior deficits were observed after heme or autologous blood injection in comparison to sham-operated controls. In addition, behavior deficits and IL-1β production were reduced in Nlrp3 knockout mice in comparison to wild-type mice. Conclusions: Our results show that intracerebral heme injection induces neuroinflammation, and neurological deficits, in an NLRP3-dependent manner, suggesting that this is a feasible model to evaluate the role of heme in neurological disorders.

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