Behavioural Brain Research 175 (2006) 82–89
Research report
Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats
Crystal L. MacLellan
a,∗
, Selina Gyawali
a
, Frederick Colbourne
a,b
a
Department of Psychology, P-217 Biological Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2E9
b
Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Received 7 April 2006; received in revised form 30 July 2006; accepted 2 August 2006
Available online 7 September 2006
Abstract
The infusion of autologous blood into the brain of rats is a widely used model of intracerebral hemorrhage (ICH). Careful assessment of functional
recovery is an essential part of preclinical testing (e.g., putative cytoprotectants). However, few tests detect long-term deficits in this model. In this
study, we used the staircase and single pellet tests to characterize skilled reaching ability after striatal ICH. Rats were trained to reach for food
pellets in these tasks before ICH, which was created by infusing 100 L of autologous blood into the striatum. We assessed reaching success in
both tasks for 5 days starting 7 and 28 days after ICH. We counted the number of reaching attempts made with each forelimb in the staircase task
and performed kinematic analysis of reaching in the single pellet task. The contralateral (to lesion) forelimb reaching success was significantly
impaired in the staircase task 1 week after ICH, but this recovered to pre-surgical levels thereafter. Reaching deficits in the single pellet task
were more severe and persistent. Detailed analysis of reaches on day 11 revealed several abnormalities in the following movement components:
pronation, grasping, supinating the paw and releasing the pellet. At 1 month, only digit opening and supination were impaired. Accordingly, the
single pellet task is better at detecting long-term skilled reaching impairments in the whole blood model of ICH. Thus, the single pellet task seems
suited to cytoprotection and rehabilitation studies.
© 2006 Elsevier B.V. All rights reserved.
Keywords: Intracerebral hemorrhage; Striatum; Neuroprotection; Recovery; Grasping; Stroke
Intracerebral hemorrhage (ICH) is one of the deadliest types
of stroke and survivors (∼60% of ICH patients) are often left
with significant disability [2,9]. For instance, arm and digit
movements necessary for reaching and grasping are persis-
tently impaired in stroke patients [4,21]. Likewise, motor sys-
tem injury in rodents, including damage to the lateral striatum
[20,32], impairs skilled reaching ability. Over the past decade,
there has been a surge of studies identifying the mechanisms
of brain injury after ICH and in testing prospective therapies
[1]. Although many experimental ICH studies report promising
therapeutic results, there has been little translation to the clinic
[1]. This failure is likely due to limitations in both experimental
and clinical practices, which have been identified for ischemia
[14,36] and ICH studies [1]. In particular, experimental studies
often fail to use long survival times and do not comprehensively
assess behavioural outcome. Given that functional recovery is
the endpoint of greatest clinical concern, it makes sense that
∗
Corresponding author. Tel.: +1 780 492 7142; fax: +1 780 492 1768.
E-mail address: clmac@ualberta.ca (C.L. MacLellan).
recovery should be rigorously assessed in preclinical studies
[6,7,19].
Researchers have examined many sensory and motor tests in
rodent stroke models [8,18,33]. An ideal test should not only
detect the presence of a lesion, but must also detect therapeu-
tic effects. Recently, we [22] characterized neurological deficits
after ICH induced by striatal infusion of bacterial collagenase,
which causes bleeding by disrupting cerebral microvasculature
[35]. Although the majority of the tests (e.g., skilled reaching,
walking and neglect) detected ICH injury, few distinguished
among gradations in injury [22]. Interestingly, the staircase task
of skilled reaching was one of the most useful tests for detecting
ICH injury and moderate differences in lesion size. However,
functional performance on a battery of tests, rather than any
single test, best predicted histological outcome 1 month after
ICH.
An alternative rodent model of ICH, induced by infusing
autologous blood into the brain [34], is routinely used to study
of the pathophysiology of ICH (for review, see [43]) and in
some cytoprotection studies (e.g., [24]). The infusion of blood,
rather than collagenase, better mimics the single large bleed
0166-4328/$ – see front matter © 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.bbr.2006.08.001