Rodent models of intracerebral hemorrhage.
The collagenase and whole blood intracerebral hemorrhage (ICH) models are widely used to identify mechanisms of injury and to evaluate treatments. Despite preclinical successes, to date, no treatment tested in phase III clinical trials has benefited ICH patients. These failures call into question the predictive value of current ICH models. By highlighting differences between these common rodent models of ICH, we sought to help investigators choose the more appropriate model for their study and to encourage the use of both whenever possible. For instance, we previously reported substantial differences in the bleeding profile, progression of cell death, and functional outcome between these models. These and other differences influence the efficacy and mechanisms of action of various treatment modalities. Thus, in this review, we also summarize neuroprotective and rehabilitation findings in each model. We conclude that differences between ICH models along with our current inability to identify the more clinically predictive model necessitate that preclinical assessments should normally be done in both. Such an approach, coupled with better assessment practices, will likely improve chances of future clinical success.
MacLellan
Crystal L
CL
Department of Psychology, University of Alberta, Edmonton, Alberta, Canada. clmac@ualberta.ca
Silasi
Gergely
G
Auriat
Angela M
AM
Colbourne
Frederick
F
D000818:Animals; D002543:Cerebral Hemorrhage / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D051381:Rats