A translationally relevant thromboembolic stroke model for the study of secondary hemorrhage after thrombolysis in rats.

Abstract:

:Secondary hemorrhage after thrombolysis in ischemic stroke is an important complication, which has been difficult to study in preclinical disease models. We have established and characterized a model of thromboembolic middle cerebral artery occlusion in rats. Advantages of this model include a very low rate of spontaneous recanalization and good reperfusion after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). In vivo T2* MR imaging and postmortem assays were used for quantification of secondary brain hemorrhage. In our protocol, 12 thrombin-induced autologous blood clots are injected into the internal carotid artery. No spontaneous reperfusion occurs in the first 24h. However, injection of rt-PA 2 or 4h thereafter leads to reperfusion of the MCA territory consistent infarcts, increased blood-brain barrier permeability, and secondary hemorrhage. Remarkably, clinically important factors known to affect the extent and likelihood of secondary hemorrhage such as hypertension and delayed onset of thrombolysis also increase hematoma size in the model. Thus, the model may serve to investigate the pathophysiology of thrombolysis-induced hemorrhage in thromboembolic ischemia as well as potential adjunctive therapies to prevent this complication.

journal_name

Brain Res

journal_title

Brain research

authors

Sun L,Zhou W,Heiland S,Marti HH,Veltkamp R

doi

10.1016/j.brainres.2010.10.067

subject

Has Abstract

pub_date

2011-01-12 00:00:00

pages

346-54

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(10)02336-X

journal_volume

1368

pub_type

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