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Lasting pure-motor deficits after focal posterior internal capsule white-matter infarcts in rats
Francesco Blasi1, Michael J Whalen2, Cenk Ayata3
1Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Abstract:
Small white-matter infarcts of the internal capsule are clinically prevalent but underrepresented among currently available animal models of ischemic stroke. In particular, the assessment of long-term outcome, a primary end point in clinical practice, has been challenging due to mild deficits and the rapid and often complete recovery in most experimental models. We, therefore, sought to develop a focal white-matter infarction model that can mimic the lasting neurologic deficits commonly observed in stroke patients. The potent vasoconstrictor endothelin-1 (n=24) or vehicle (n=9) was stereotactically injected into the internal capsule at one of three antero-posterior levels (1, 2, or 3 mm posterior to bregma) in male Sprague-Dawley rats. Endothelin-injected animals showed highly focal (~1 mm(3)) and reproducible ischemic infarcts, with severe axonal and myelin loss accompanied by cellular infiltration when examined 2 and 4 weeks after injection. Only those rats injected with endothelin-1 at the most posterior location developed robust and pure-motor deficits in adhesive removal, cylinder and foot-fault tests that persisted at 1 month, without detectable sensory impairments. In summary, we present an internal capsule stroke model optimized to produce lasting pure-motor deficits in rats that may be suitable to study neurologic recovery and rehabilitation after white-matter injury.
Insights
Researchers developed a new rat model for internal capsule stroke, causing lasting motor deficits. This model better mimics human stroke outcomes for studying recovery and rehabilitation after white-matter injury.
Area of Science:
- Neuroscience
- Neurology
- Stroke Research
Background:
- Small white-matter infarcts in the internal capsule are common in clinical stroke but poorly represented in current animal models.
- Existing models often show rapid recovery, hindering the study of long-term outcomes and rehabilitation.
Purpose of the Study:
- To develop a focal white-matter infarction model in rats that replicates lasting neurological deficits seen in human stroke patients.
- To create a reliable model for studying white-matter injury, neurologic recovery, and rehabilitation.
Main Methods:
- Stereotactic injection of endothelin-1 (a vasoconstrictor) or vehicle into the internal capsule of male Sprague-Dawley rats at specific posterior locations.
- Assessment of infarct size, axonal/myelin loss, and cellular infiltration at 2 and 4 weeks post-injection.
- Evaluation of motor deficits using adhesive removal, cylinder, and foot-fault tests at 1 month.
Main Results:
- Endothelin-1 injection created focal, reproducible ischemic infarcts (~1 mm³) with significant axonal and myelin loss.
- Rats injected at the most posterior location (3 mm posterior to bregma) developed persistent, pure-motor deficits.
- No significant sensory impairments were detected in the developed model.
Conclusions:
- A novel internal capsule stroke model in rats has been established, producing lasting pure-motor deficits.
- This model effectively mimics long-term outcomes of white-matter stroke, suitable for studying recovery and rehabilitation.
- The model's reproducibility and focus on motor deficits offer a valuable tool for preclinical stroke research.
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