Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage

Nakamura, Takehiro; Keep, Richard F.; Hua, Ya; Schallert, Timothy; Hoff, Julian T.; Xi, Guohua

doi:10.3171/jns.2004.100.4.0672

Cited by 267 publications

(118 citation statements)

References 36 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Several studies have shown that hemoglobin and its degradation products, in particular iron, resulting from erythrocyte lysis after ICH exert neurotoxic effects and contribute to the development and progression of brain edema following ICH and that treatment with iron chelators can reduce these effects [1,2,3,4, 16, 17]. There have not been many clinical studies examining the status and role of iron in the brain.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Hematoma Iron Content and Perihematoma Edema: An MRI Study

2009

View full text Add to dashboard Cite

Background: Iron neurotoxicity has been linked to delayed neuronal injury and edema formation after intracerebral hemorrhage (ICH). We have previously shown that serum ferritin, an indicator of body iron load, correlates with the relative perihematoma edema volume (RPHEV) on days 3–4 after ICH. We undertook this study to directly examine the relationship between in vivo brain and hematoma iron content, measured by MRI, and RPHEV. Methods: We retrospectively reviewed prospectively collected clinical and laboratory data from 36 consecutive patients with acute spontaneous lobar ICH who had MRI performed within 2–4 days of ICH onset. We measured hematoma and edema volumes, and the signal intensity on T₂-weighted images (T₂SI), as an estimate of iron content, in the hematoma and contralateral globus pallidus (GP). We calculated the RPHEV and T₂SI in the hematoma and GP, relative to T₂SI in the frontal deep white matter which contains negligible iron, to estimate the hematoma and brain iron load. We used Spearman correlation coefficient to determine the association of relative T₂SI of the hematoma and GP with RPHEV. Results: We found a significant inverse correlation between the relative T₂SI in the hematoma (r = –0.75, p < 0.001) and to a lesser extent in the GP (r = –0.34, p = 0.04) and the RPHEV. Conclusions: Our findings suggest that in vivo brain and hematoma iron content, as measured by MRI, is linked to perihematoma edema after ICH, and provide further support to existing preclinical evidence linking iron-mediated toxicity to delayed neuronal injury after ICH.

show abstract

Section: Discussionmentioning

confidence: 99%

The Relationship between Hematoma Iron Content and Perihematoma Edema: An MRI Study

2009

View full text Add to dashboard Cite

show abstract

“…Erythrocyte lysis occurs within 24 hours after ICH, peaking at day 1 to 7 (Nakamura et al, 2004; Wu et al, 2003; Xi et al, 2006), and hemoglobin- and iron-mediated brain injuries occur along with lysis of extravasated erythrocytes. Injection of hemoglobin and its degradation products into striatum also cause brain damage (Hua et al, 2003; Huang et al, 2002).…”

Section: Primary and Secondary Brain Injury After Ichmentioning

confidence: 99%

Intercellular cross-talk in intracerebral hemorrhage

et al. 2015

Self Cite

View full text Add to dashboard Cite

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high mortality and morbidity. Currently, there are few treatment strategies for ICH-induced brain injury. A recent increase in interest in the pathophysiology of ICH, has led to elucidation of the pathways underlying ICH-induced brain injury, pathways where intercellular and hematoma to cell signaling play important roles. In this review, we summarize recent advances in ICH research focusing on intercellular and hematoma:cell cross-talk related to brain injury and recovery after ICH.

show abstract

“…(4, 5) In animal models of ICH, PHE is consistently associated with worse neurological outcome. (6) Currently, however, the relationship between PHE and outcome in ICH patients is controversial, since studies examining this question have shown conflicting results. (7, 8) This critical gap in knowledge severely impedes translation of novel therapies for ICH.…”

Section: Introductionmentioning

confidence: 99%

Rate of Perihematomal Edema Expansion Predicts Outcome After Intracerebral Hemorrhage

Urday

Beslow

Dai

et al. 2016

Critical Care Medicine

100

View full text Add to dashboard Cite

Objective Intracerebral hemorrhage (ICH) is a devastating disorder with no current treatment. Whether peri-hematomal edema (PHE) is an independent predictor of neurologic outcome is controversial. We sought to determine whether PHE expansion rate predicts outcome after ICH. Design Retrospective cohort study Setting Tertiary medical center Patients 139 consecutive supratentorial spontaneous ICH patients >18 years admitted between 2000–2013. Interventions None Measurements and Main Results ICH, intraventricular hemorrhage (IVH), and PHE volumes were measured from computed tomography (CT) scans obtained at presentation, 24 hours, and 72 hours post-ICH. PHE expansion rate was the difference between initial and follow-up PHE volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) PHE expansion rate at 24 hours and 90-day mortality and 2) PHE expansion rate at 24 hours and 90-day modified Rankin Scale score (mRS). PHE expansion rate between admission and 24-hours post-ICH was a significant predictor of 90-day mortality (OR 2.97, 95%CI 1.48–5.99, p=0.002). This association persisted after adjusting for all components of the ICH score (OR 2.21, 95% CI 1.05–4.64, p=0.04). Similarly, higher 24-hour PHE expansion rate was associated with poorer mRS in an ordinal shift analysis (OR 2.40, 95% CI 1.37–4.21, p=.002), even after adjustment for all ICH score components (OR 2.07, 95% CI 1.12–3.83, p=0.02). Conclusions Faster PHE expansion rate 24 hours post-ICH is associated with worse outcome. PHE may represent an attractive translational target for secondary injury after ICH.

show abstract

Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage

Abstract: Deferoxamine and other iron chelators may be potential therapeutic agents for ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.

Cited by 267 publications

References 36 publications

The Relationship between Hematoma Iron Content and Perihematoma Edema: An MRI Study

The Relationship between Hematoma Iron Content and Perihematoma Edema: An MRI Study

Intercellular cross-talk in intracerebral hemorrhage

Rate of Perihematomal Edema Expansion Predicts Outcome After Intracerebral Hemorrhage

Contact Info

Product

Resources

About