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(Stroke. 2008;39:3405.)
© 2008 American Heart Association, Inc.

Original Contributions

Reperfusion-Associated Hemorrhagic Transformation in SHR Rats

Evidence of Symptomatic Parenchymal Hematoma

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

From the Sections on Stroke Diagnostics and Therapeutics (E.C.H., L.L.L., S.W.) and Clinical Investigations (J.M.H.), and the Stroke Branch (E.C.H., L.L.L., J.M.H., S.W.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.

Correspondence to Erica C. Henning, PhD, Section on Stroke Diagnostics and Therapeutics, Stroke Branch, National Institute of Neurological Disorders and Stroke, Building 10, Room B1D733, 10 Center Dr, MSC 1063, Bethesda, MD 20892. E-mail henninge{at}ninds.nih.gov

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).

Key Words: stroke • reperfusion • hemorrhagic transformation • parenchymal hematoma • spontaneously hypertensive rats • middle cerebral artery occlusion