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Updated: May 9, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke
S A Lowrance1,2, K D Fink1,2, A Crane1,2
1Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.
Insights
The endothelin-1 (ET-1) stroke model in rats caused cognitive deficits, which were effectively measured by the spatial operant reversal task (SORT). Bone-marrow-derived mesenchymal stem cells (BMMSCs) treatment attenuated these stroke-induced memory impairments.
Area of Science:
- Neuroscience
- Regenerative Medicine
Background:
- Stroke is a leading cause of death and disability, often resulting in cognitive impairments.
- Current animal models struggle to accurately replicate chronic cognitive deficits seen in human stroke patients.
Purpose of the Study:
- To validate the endothelin-1 (ET-1) induced stroke model for chronic cognitive deficits.
- To assess the efficacy of the spatial operant reversal task (SORT) in measuring these deficits.
- To investigate the therapeutic potential of bone-marrow-derived mesenchymal stem cells (BMMSCs) in mitigating stroke-related cognitive dysfunction.
Main Methods:
- Rats received unilateral intracerebral injections of ET-1 or vehicle to induce stroke.
- BMMSCs or vehicle were administered intrastriatally seven days post-stroke.
- Cognitive function was evaluated using a novel SORT designed to differentiate memory deficits from motor impairments.
Main Results:
- ET-1 treated rats exhibited significantly increased cognitive errors on the SORT six weeks post-stroke.
- BMMSC transplantation successfully attenuated the observed cognitive deficits in the stroke model.
Conclusions:
- The ET-1 model effectively replicates chronic cognitive deficits post-stroke.
- The SORT is a reliable tool for assessing stroke-induced cognitive impairments without motor confounds.
- BMMSCs show promise as a potential treatment for cognitive dysfunction following stroke.
Purpose:
Stroke is the third leading cause of death and permanent disability in the United States, often producing long-term cognitive impairments, which are not easily recapitulated in animal models. The goals of this study were to assess whether: (1) the endothelin-1 (ET-1) model of chronic stroke produced discernable cognitive deficits; (2) a spatial operant reversal task (SORT) would accurately measure memory deficits in this model; and (3) bone-marrow-derived mesenchymal stem cells (BMMSCs) could reduce any observed deficits.
Methods:
Rats were given unilateral intracerebral injections of vehicle or ET-1, a stroke-inducing agent, near the middle cerebral artery. Seven days later, they were given intrastriatal injections of BMMSCs or vehicle, near the ischemic penumbra. The cognitive abilities of the rats were assessed on a novel SORT, which was designed to efficiently distinguish cognitive deficits from potential motoric confounds.
Results:
Rats given ET-1 had significantly more cognitive errors at six weeks post-stroke on the SORT, and that these deficits were attenuated by BMMSC transplants.
Conclusions:
These findings indicate that: (1) the ET-1 model produces chronic cognitive deficits; (2) the SORT efficiently measures cognitive deficits that are not confounded by motoric impairment; and (3) BMMSCs may be a viable treatment for stroke-induced cognitive dysfunction.
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