Hemorrhage into Embolic Brain Infarcts

Caplan, Louis R.

doi:10.1592/phco.19.3.125.30926

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…19 Hematoma and petechiae were counted per volume of brain, and the total number of petechiae in infarcted area estimated ICH severity. Other adjacent sections were stained with cresyl fast violet to blindly quantify infarct and hemispheric volumes (mm 3 ).…”

Section: Assessment Of Ich and Infarctionmentioning

confidence: 99%

“…There were 2 types of hemorrhagic transformation: (1) hemorrhagic infarction, identified as petechiae, and (2) parenchymal hemorrhage, identified as hematoma. 19 Hematoma and petechiae were counted per volume of brain, and the total number of petechiae in infarcted area estimated ICH severity. Other adjacent sections were stained with cresyl fast violet to blindly quantify infarct and hemispheric volumes (mm 3 ).…”

Section: Assessment Of Ich and Infarctionmentioning

confidence: 99%

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Involvement of Thrombolysis in Recombinant Tissue Plasminogen Activator-Induced Cerebral Hemorrhages and Effect on Infarct Volume and Postischemic Endothelial Function

Gautier¹,

Pétrault²,

Gelé³

et al. 2003

Stroke

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Background and Purpose-In a model of mechanical focal ischemia, we investigated the involvement of thrombolysis products (TLP) in recombinant tissue plasminogen activator (rtPA)-induced intracerebral complications and the effects on infarct volume and postischemic endothelial function. Methods-Hemorrhage incidence and severity were evaluated by histomorphometric analysis in male spontaneously hypertensive rats (SHR) subjected to 60-minute intraluminal middle cerebral artery (MCA) occlusion and receiving intravenously 5 hours later either saline, rtPA (3, 10, or 30 mg/kg), or rtPA (10 mg/kg) associated with TLP (rtPAϩTLP). In addition, MCA reactivity was assessed in rtPA-or rtPAϩTLP-treated SHR versus control Wistar-Kyoto rats or SHR. Results-No hemorrhage was observed visually in SHR receiving saline. In contrast, rtPA administration induced hemorrhagic complications in infarcted areas in a dose-independent manner. Administration of rtPAϩTLP solution, containing a high concentration of plasmin, did not affect hemorrhage incidence but significantly increased hemorrhage severity (8.8Ϯ2.3 petechiae versus 3.0Ϯ1.0 petechiae in rtPA group; PϽ0.001). This increased severity was associated with a significant increase of both infarct volume (182Ϯ10 versus 144Ϯ15 mm 3 in rtPA group; PϽ0.01) and postischemic impairment of MCA endothelium-dependent relaxation (9Ϯ0.5% versus 13Ϯ1% in rtPA group; PϽ0.05). Key Words: hemorrhage Ⅲ ischemia, focal Ⅲ plasmin Ⅲ thrombolysis Ⅲ tissue plasminogen activator T hrombolytic therapy with recombinant tissue plasminogen activator (rtPA) has demonstrated improvement in clinical outcome in acute ischemic stroke. 1,2 However, the threat of intracerebral hemorrhage (ICH) is an important barrier to widespread administration of thrombolytic agents. While many factors, such as elevated blood pressure, diabetes, age, and rtPA administration time, contribute to the occurrence of ICH, the underlying mechanisms remain elusive. [3][4][5] ICH are preferentially located in the infarct area, suggesting a role of ischemia per se. 6,7 In response to ischemic and inflammatory stimuli, vascular modifications may also be involved in ICH pathophysiology. 8 In particular, endothelium-dependent relaxation, a marker of ischemia-induced impairment of cerebral vasculature, 9,10 is worsened in vitro by the application of rtPA. 11 It remains unknown whether rtPA directly induces ICH or if the interaction between rtPA and thrombus, via the resulting thrombolysis products (TLP), is involved. Existence of rtPA-induced ICH in thromboembolic models has been well established, 7,12-15 whereas it remains more uncertain in mechanical models of ischemia. 6,16 The difference between the 2 models suggests that thrombus may contribute to the occurrence of ICH. To test this hypothesis, we compared the effects of rtPA or rtPA-induced TLP in a model of mechanical middle cerebral artery (MCA) occlusion on ICH incidence and severity. We also studied infarct volume and MCA endothelial function to investigate the mechanism of ICH occur...

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Section: Assessment Of Ich and Infarctionmentioning

confidence: 99%

Section: Assessment Of Ich and Infarctionmentioning

confidence: 99%

Involvement of Thrombolysis in Recombinant Tissue Plasminogen Activator-Induced Cerebral Hemorrhages and Effect on Infarct Volume and Postischemic Endothelial Function

Gautier¹,

Pétrault²,

Gelé³

et al. 2003

Stroke

View full text Add to dashboard Cite

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“…Those macroscopic hemorrhages are of particular interest as they impact the neurological deficit [30]. Slices collected at the same levels were stained with cresyl violet, and the infarct volumes were quantified blindly.…”

Section: Methodsmentioning

confidence: 99%

Combined therapy with PJ34, a poly(ADP‐ribose)polymerase inhibitor, reduces tissue plasminogen activator‐induced hemorrhagic transformations in cerebral ischemia in mice

Haddad

Coqueran

Plotkine

et al. 2012

Fundamemntal Clinical Pharma

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Recombinant tissue-type plasminogen activator (rt-PA) is presently the only pharmacological treatment approved for thrombolysis in patients suffering from ischemic stroke. Although reperfusion of ischemic tissue is essential, the use of rt-PA is limited due to its narrow therapeutic window and risk of hemorrhagic transformations. Recent studies have shown that rt-PA amplifies the post-ischemic activation of the nuclear enzyme poly(ADP-ribose)polymerase (PARP). This enzyme has been shown to contribute to both the breakdown of the blood brain barrier and spontaneous hemorrhagic transformations after ischemia. We therefore examined the capacity of PJ34 (N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino) acetamide hydrochloride), a potent inhibitor of PARP, to reduce the hemorrhagic transformations that occur after rt-PA in mice with permanent focal cerebral ischemia. Ischemia was produced by intraluminal occlusion of the left middle cerebral artery and treated with vehicle, rt-PA (10 mg/kg, i.v., 6 h after occlusion) or rt-PA plus PJ34 (3, 6 or 12 mg/kg, i.p., at ischemia onset and 4 h later). Hemorrhagic transformations, neurological examination, and infarct volumes were evaluated 48 h after the onset of ischemia. Delayed administration of rt-PA resulted in increased hemorrhagic transformations and aggravated the neurological deficit. Giving PJ34 (3 mg/kg) markedly reduced the hemorrhagic transformations, an effect not owing to a modification of matrix metalloprotease activity. Furthermore, PJ34 improved the neurological functions of rt-PA-treated ischemic mice. To conclude, the PARP inhibitor PJ34 makes rt-PA safer in experimental ischemic stroke.

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Simulation of Intracranial Acoustic Fields in Clinical Trials of Sonothrombolysis

Baron

Aubry

Tanter

et al. 2009

Ultrasound in Medicine & Biology

121

107

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Hemorrhage into Embolic Brain Infarcts

Cited by 4 publications

References 9 publications

Involvement of Thrombolysis in Recombinant Tissue Plasminogen Activator-Induced Cerebral Hemorrhages and Effect on Infarct Volume and Postischemic Endothelial Function

Involvement of Thrombolysis in Recombinant Tissue Plasminogen Activator-Induced Cerebral Hemorrhages and Effect on Infarct Volume and Postischemic Endothelial Function

Combined therapy with PJ34, a poly(ADP‐ribose)polymerase inhibitor, reduces tissue plasminogen activator‐induced hemorrhagic transformations in cerebral ischemia in mice

Simulation of Intracranial Acoustic Fields in Clinical Trials of Sonothrombolysis

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