Hemorrhagic Transformation during Thrombolytic Therapy and Reperfusion: Effects of Age, Blood Pressure, and Matrix Metalloproteinases

Lyden, Patrick D.

doi:10.1016/j.jstrokecerebrovasdis.2013.02.001

Cited by 12 publications

(9 citation statements)

References 36 publications

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“…50 These findings are consistent with animal stroke models that have found increasing age, hypertension, and blood glucose predispose to HT. [140][141][142] Clinical Factors: Age, Hypertension, Hyperglycemia, and Hemorrhagic Transformation Increasing age has frequently been associated with an increased risk of HT in patients with stroke. 8,26,50,[143][144][145][146][147][148] The mechanisms by which age may contribute to HT are unclear.…”

Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

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Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

461

369

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Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, we summarize studies of HT in both animals and humans. We propose that early HT (o18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood-brain barrier (BBB) disruption. This contrasts to delayed HT (418 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.

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Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

“…However, in normotensive rats age did increase the rate of HT. 140 Increased serum glucose is associated with an increase risk of HT in stroke patients. In transient MCAO rat models, acute hyperglycemia increases BBB disruption and the rate of HT.…”

Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

461

369

View full text Add to dashboard Cite

show abstract

“…Diabetes causes tremendous edema due to several factors including enhanced protein kinase C activation and higher oxidative stress [68]. Similarly, hypertension is associated with increased vascular endothelial growth (VEGF) and oxidative stress that can increase both hemorrhage and edema [70,71]. Thus, agents on board that inhibit these processes prior to recanalization with ET or IA delivery of these agents during ET (see below) could be effective at preventing reperfusion injury.…”

Section: Targeting Recanalization and Reperfusion As A Neuroprotectivmentioning

confidence: 99%

Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy

Linfante

Cipolla

2016

Transl. Stroke Res.

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Recent positive clinical trials using mechanical thrombectomy proved that endovascular recanalization is an effective treatment for patients with acute stroke secondary to large vessel occlusions. The trials offer definite evidence that in acute ischemia recanalization is a powerful predictor of good outcome. However, even in the era of rapid and effective recanalization using endovascular approaches, the percentage of patients with good outcomes varies between 33% and 71%. In addition, the number of patients who are eligible for endovascular thrombectomy is small and usually based on having salvageable tissue on imaging. There is therefore room for improvement to both enhance the effectiveness of current practice and expand treatment to a larger subset of stroke patients. In this review, we highlight some of the most promising approaches to improve endovascular therapy by combining with strategies to enhance collateral perfusion and vascular protection.

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“…Measurement errors may lead to underestimation and overestimation of the correlation between BP and prognosis. Second, only hospitalized cases were included, thus selection bias was inevitable …”

Section: Study Strengths and Limitationsmentioning

confidence: 99%

A Reasonable Blood Pressure Level for Good Clinical Outcome After the Acute Phase of Ischemic Stroke

Meng

Liu

et al. 2015

J of Clinical Hypertension

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Blood pressure (BP) levels are closely associated with clinical outcomes in patients with acute ischemic stroke, but current research data cannot yet determine what level of reasonable BP should be maintained in clinical practice. The authors conducted a prospective registered clinical trial and enrolled 873 patients admitted for the first episode of acute ischemic stroke within 24 hours from symptom onset and with normal neurological function before stroke. Analysis results showed that the highest probability of good neurological recovery was associated with the lowest risk of neurological deterioration and poor functional outcome at systolic BP (SBP) and diastolic BP (DBP) levels of 140 mm Hg to 159 mm Hg and DBP 90 mm Hg to 99 mm Hg, respectively, whereas patients with extreme hypotension (SBP <100 mm Hg /DBP <70 mm Hg) and hypertension (SBP ≥200 mm Hg /DBP ≥120 mm Hg) were associated with poor neurological recovery. Both higher and lower BP levels in the acute phase of ischemic stroke were unfavorable to neurological functional recovery (adjusted odds ratio, 1.948/1.913 and 2.129/2.022, respectively, with SBP 120–139 mm Hg as a reference). In addition, BP maintained at SBP 140 mm Hg to 159 mm Hg and DBP 90 mm Hg to 99 mm Hg within 7 days after stroke may be beneficial to neurological functional recovery.

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Hemorrhagic Transformation during Thrombolytic Therapy and Reperfusion: Effects of Age, Blood Pressure, and Matrix Metalloproteinases

Cited by 12 publications

References 36 publications

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy

A Reasonable Blood Pressure Level for Good Clinical Outcome After the Acute Phase of Ischemic Stroke

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