Original Article
Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1031–1042. doi:10.1038/sj.jcbfm.9600255; published online 14 December 2005
Gauging recovery after hemorrhagic stroke in rats: implications for cytoprotection studies
Crystal L MacLellan1, Angela M Auriat1, Steven C McGie2, Reginia H Y Yan1, Hang D Huynh1, Maxine F De Butte1 and Frederick Colbourne1,2
- 1Department of Psychology, University of Alberta, Edmonton, Alberta, Canada
- 2Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Correspondence: Dr F Colbourne, Department of Psychology, University of Alberta, P-217 Biological Sciences Building, Edmonton, Alberta, Canada T6G 2E9. E-mail: fcolbour@ualberta.ca
Received 28 September 2005; Revised 20 October 2005; Accepted 29 October 2005; Published online 14 December 2005.
Abstract
Successful clinical translation of prospective cytoprotectants will likely occur only with treatments that improve functional recovery in preclinical (rodent) studies. Despite this assumption, many rely solely on histopathologic end points or the use of one or two simple behavioral tests. Presently, we used a battery of tests to gauge recovery after a unilateral intracerebral hemorrhagic stroke (ICH) targeting the striatum. In total, 60 rats (N=15 per group) were stereotaxically infused with 0 (SHAM), 0.06 (MILD lesion), 0.12 (MODERATE lesion), or 0.18 U (SEVERE lesion) of bacterial collagenase. This created a range of injury akin to moderate (from SEVERE to MODERATE or MODERATE to MILD lesion size
30% reduction) and substantial cytoprotection (SEVERE to MILD lesion size—51% reduction). Post-ICH functional testing occurred over 30 days. Tests included the horizontal ladder and elevated beam tests, swimming, limb-use asymmetry (cylinder) test, a Neurologic Deficit Scale, an adhesive tape removal test of sensory neglect, and the staircase and single pellet tests of skilled reaching. Most tests detected significant impairments (versus SHAM), but only a few (e.g., staircase) frequently distinguished among ICH groups and none consistently differentiated among all ICH groups. However, by using a battery of tests we could behaviorally distinguish groups. Thus, preclinical testing would benefit from using a battery of behavioral tests as anything less may miss treatment effects. Such testing must be based on factors including the type of lesion, the postoperative delay and the time required to complete testing.
Keywords:
motor system, neuroprotection, rodent, striatum
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