Iron Toxicity in Intracerebral Hemorrhage: Physiopathological and Therapeutic Implications

Author(s):  
Yufei Wei ◽  
Xiaoxiao Song ◽  
Ying Gao ◽  
Yonghong Gao ◽  
Yuanyuan Li ◽  
...  
Author(s):  
Kaori Miwa ◽  
Masatoshi Koga ◽  
Mayumi Fukuda‐Doi ◽  
Haruko Yamamoto ◽  
Kanata Tanaka ◽  
...  

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01176565.


2010 ◽  
Vol 31 (5) ◽  
pp. 1243-1250 ◽  
Author(s):  
He Wu ◽  
Tao Wu ◽  
Xueying Xu ◽  
Jessica Wang ◽  
Jian Wang

Intracerebral hemorrhage (ICH) is a devastating form of stroke. In this study, we examined the efficacy of deferoxamine (DFX), an iron chelator, after collagenase-induced ICH in 12-month-old mice. Intracerebral hemorrhage was induced by intrastriatal injection of collagenase. Deferoxamine (200 mg/kg, intraperitoneal) or vehicle was administrated 6 hours after ICH and then every 12 hours for up to 3 days. Neurologic deficits were examined on days 1 and 3 after ICH. Mice were killed after 1 or 3 days of DFX treatment for examination of iron deposition, neuronal death, oxidative stress, microglia/astrocyte activation, neutrophil infiltration, brain injury volume, and brain edema and swelling. Collagenase-induced ICH resulted in iron overload in the perihematomal region on day 3. Systemic administration of DFX decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, and reduced microglial activation and neutrophil infiltration without affecting astrocytes. Although DFX did not reduce brain injury volume, edema, or swelling, it improved neurologic function. Results of our study indicate that iron toxicity contributes to collagenase-induced hemorrhagic brain injury and that reducing iron accumulation can reduce neuronal death and modestly improve functional outcome after ICH in mice.


1992 ◽  
Vol 3 (3) ◽  
pp. 685-702 ◽  
Author(s):  
Christopher B. Shields ◽  
William A. Friedman

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S505-S505
Author(s):  
Huijin Yan ◽  
Mengzhou Xue ◽  
Christopher Power ◽  
Marc R Del-Bigio ◽  
James Peeling

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