title: Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion.
abstract: Many therapies have shown promise in preclinical stroke studies, but few benefit patients. A greater understanding of stroke pathophysiology is needed to successfully develop therapies, and this depends on appropriate animal models. The collagenase and blood infusion models of intracerebral hemorrhage (ICH) are widely used; yet, investigators often prefer using one model for a variety of reasons. Thus, we directly compared these to highlight advantages and limitations of each as well as the assessment approach. An ICH was created by infusing blood or bacterial collagenase into the rats' striatum. We matched initial hematoma volume in each model (Experiment 1) and assessed the time course of bleeding (Experiment 2). Functional deficits and the progression of injury were tracked over 6 weeks using behavior, magnetic resonance imaging, and histology (Experiment 3). Despite similar initial hematoma volumes, collagenase-induced ICH resulted in a greater blood-brain barrier breakdown and more damage to the striatum, substantia nigra, white matter, and cortex. Magnetic resonance imaging revealed faster hematoma resolution in the blood model, and little increase in the volume of tissue lost from 1 to 6 weeks. In contrast, tissue loss continued over 4 weeks in the collagenase model. Finally, functional deficits recovered more quickly and completely in the blood model. This study highlights key differences between these models and that neither closely replicates the human condition. Thus, both should be used whenever possible taking into account the significant differences between these models and their limitations. Furthermore, this work illustrates significant weaknesses with several outcome measures.
authors.affiliation: Department of Psychology and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: MacLellan
authors.forename: Gergely
authors.initials: G
authors.lastname: Silasi
authors.forename: Candice C
authors.initials: CC
authors.lastname: Poon
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Edmundson
authors.forename: Richard
authors.initials: R
authors.lastname: Buist
authors.forename: James
authors.initials: J
authors.lastname: Peeling
authors.forename: Frederick
authors.initials: F
authors.lastname: Colbourne
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology; D017364:Collagenases / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D006406:Hematoma; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D065227:Transfusion Reaction
chemical_list: D017364:Collagenases