Blood Injection Intracerebral Hemorrhage Pig Model

Author(s):  
Yuxiang Gu ◽  
Shenglong Cao ◽  
Guohua Xi ◽  
Ya Hua
2018 ◽  
Vol 38 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Muhammad E Haque ◽  
Refaat E Gabr ◽  
Xiurong Zhao ◽  
Khader M Hasan ◽  
Andrew Valenzuela ◽  
...  

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.


Author(s):  
Yuxiang Gu ◽  
Ya Hua ◽  
Yangdong He ◽  
Lin Wang ◽  
Hua Hu ◽  
...  

Author(s):  
Lauren H. Sansing ◽  
Scott E. Kasner ◽  
Louise McCullough ◽  
Puneet Agarwal ◽  
Frank A. Welsh ◽  
...  

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Muhammad E Haque ◽  
Refaat E Gabr ◽  
Xiurong Zhao ◽  
Khader M Hasan ◽  
Ponnada A Narayana ◽  
...  

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.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Xiang Zhou ◽  
Qing Xie ◽  
Guohua Xi ◽  
Richard F Keep ◽  
Ya Hua

Differentiation 47 (CD47) has a role in ischemic brain injury and phagocytosis. The role of CD47 in intracerebral hemorrhage (ICH) has not been investigated and the current study examined brain CD47 expression in a piglet ICH model. Methods: Piglets received a blood injection or needle insertion into the right frontal lobe and were euthanized at different times to examine CD47 expression. Piglets were also treated with an iron chelator, deferoxamine, (50 mg/kg, i.m.) or vehicle and euthanized at day-3 to examine the effects on CD47. Results: ICH resulted in upregulation of brain CD47 in both white and grey matter by both immunohistochemistry and Western blot. A time-course showed ICH-induced CD47 upregulation from 4 hours to day-14. ICH-induced CD47 upregulation peaked at day-3. CD47 positive cells were neurons, microglia/macrophage and oliogodendrocytes. Systemic treatment with deferoxamine (started at 2 hours after ICH and every 12 hours for 3 days), an iron chelator, reduced CD47 levels in the ipsilateral white matter (CD47/beta-actin: 0.35 ± 0.08 vs. 0.73 ± 0.09 in vehicle-treated pigs, p<0.01) and grey matter (0.64 ± 0.16 vs.1.19 ± 0.20 in vehicle-treated pigs, p<0.01) at day-3 after ICH. CD47 expression on erythrocytes was reduced at 24 hours compared with that at 4 hours after ICH (p<0.05), and significant erythrophagocytosis was present in the clot. Conclusion: CD47 expression was increased in the perihematomal white and grey matter and was decreased in the clot after ICH. Alterations in CD47 expression may play a role in parenchymal injury and hematoma resolution. Deferoxamine and iron may modulate CD47 expression. Key words: cerebral hemorrhage, CD47, deferoxamine, erythrophagocytosis, piglets


2019 ◽  
Vol 13 ◽  
Author(s):  
Muhammad E. Haque ◽  
Refaat E. Gabr ◽  
Sarah D. George ◽  
Xiurong Zhao ◽  
Seth B. Boren ◽  
...  

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