Reperfusion-associated hemorrhagic transformation in SHR rats: Evidence of symptomatic parenchymal hematoma

Erica C. Henning, Lawrence L. Latour, John M. Hallenbeck, Steven Warach

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background and Purpose: Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Methods: Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T2-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, ≤30% lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, >30% lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Results: Final hemorrhage scores based on severity were as follows: HI-1 23.1%, HI-2 30.8%, PH-1 30.8%, and PH-2 15.4%. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. Conclusions: This model has a high incidence of parenchymal hematomas (46.2%) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially "at risk" for neurologic deterioration (PH-1).

Original languageEnglish (US)
Pages (from-to)3405-3410
Number of pages6
JournalStroke
Volume39
Issue number12
DOIs
StatePublished - Dec 1 2008

Fingerprint

Inbred SHR Rats
Hematoma
Reperfusion
Hemorrhage
Nervous System
Edema
Magnetic Resonance Imaging
Middle Cerebral Artery Infarction
Incidence
Tissue Plasminogen Activator
Blood-Brain Barrier
Sutures
Weight Loss
Ischemia
Therapeutics

Keywords

  • Hemorrhagic transformation
  • Middle cerebral artery occlusion
  • Parenchymal hematoma
  • Reperfusion
  • Spontaneously hypertensive rats
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Reperfusion-associated hemorrhagic transformation in SHR rats : Evidence of symptomatic parenchymal hematoma. / Henning, Erica C.; Latour, Lawrence L.; Hallenbeck, John M.; Warach, Steven.

In: Stroke, Vol. 39, No. 12, 01.12.2008, p. 3405-3410.

Research output: Contribution to journalArticle

Henning, Erica C. ; Latour, Lawrence L. ; Hallenbeck, John M. ; Warach, Steven. / Reperfusion-associated hemorrhagic transformation in SHR rats : Evidence of symptomatic parenchymal hematoma. In: Stroke. 2008 ; Vol. 39, No. 12. pp. 3405-3410.
@article{829530517b224fd99beb1793907ecf1c,
title = "Reperfusion-associated hemorrhagic transformation in SHR rats: Evidence of symptomatic parenchymal hematoma",
abstract = "Background and Purpose: Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Methods: Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T2-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, ≤30{\%} lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, >30{\%} lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Results: Final hemorrhage scores based on severity were as follows: HI-1 23.1{\%}, HI-2 30.8{\%}, PH-1 30.8{\%}, and PH-2 15.4{\%}. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. Conclusions: This model has a high incidence of parenchymal hematomas (46.2{\%}) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially {"}at risk{"} for neurologic deterioration (PH-1).",
keywords = "Hemorrhagic transformation, Middle cerebral artery occlusion, Parenchymal hematoma, Reperfusion, Spontaneously hypertensive rats, Stroke",
author = "Henning, {Erica C.} and Latour, {Lawrence L.} and Hallenbeck, {John M.} and Steven Warach",
year = "2008",
month = "12",
day = "1",
doi = "10.1161/STROKEAHA.108.520304",
language = "English (US)",
volume = "39",
pages = "3405--3410",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Reperfusion-associated hemorrhagic transformation in SHR rats

T2 - Evidence of symptomatic parenchymal hematoma

AU - Henning, Erica C.

AU - Latour, Lawrence L.

AU - Hallenbeck, John M.

AU - Warach, Steven

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Background and Purpose: Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Methods: Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T2-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, ≤30% lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, >30% lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Results: Final hemorrhage scores based on severity were as follows: HI-1 23.1%, HI-2 30.8%, PH-1 30.8%, and PH-2 15.4%. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. Conclusions: This model has a high incidence of parenchymal hematomas (46.2%) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially "at risk" for neurologic deterioration (PH-1).

AB - Background and Purpose: Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Methods: Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T2-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, ≤30% lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, >30% lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Results: Final hemorrhage scores based on severity were as follows: HI-1 23.1%, HI-2 30.8%, PH-1 30.8%, and PH-2 15.4%. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. Conclusions: This model has a high incidence of parenchymal hematomas (46.2%) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially "at risk" for neurologic deterioration (PH-1).

KW - Hemorrhagic transformation

KW - Middle cerebral artery occlusion

KW - Parenchymal hematoma

KW - Reperfusion

KW - Spontaneously hypertensive rats

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=58149333282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149333282&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.108.520304

DO - 10.1161/STROKEAHA.108.520304

M3 - Article

C2 - 18757286

AN - SCOPUS:58149333282

VL - 39

SP - 3405

EP - 3410

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 12

ER -