Affiliations: [a] Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA | [b] Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA | [c] Central Michigan University College of Medicine, Mount Pleasant, MI, USA | [d] Field Neurosciences Institute, Saginaw, MI, USA
Correspondence:
[*]
Corresponding author: Gary L. Dunbar, Health Professions Building 2182, Central Michigan University, Mount Pleasant, MI 48859, USA. Tel.: +1 989 774 3282; Fax: +1 989 774 2553; [email protected]
Note: [1] Current affiliations: Nicholas D Dey at Prevacus Inc., Tallahassee FL, USA. [email protected]
Note: [2] Jessica J Matchynski at Rochester College School of Naturaland Behavioral Sciences, Rochester, MI, USA. [email protected]
Abstract:
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.
