Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke

S. A. Lowrance, Kyle Fink, A. Crane, J. Matyas, N. D. Dey, J. J. Matchynski, T. Thibo, T. Reinke, J. Kippe, C. Hoffman, M. Sandstrom, J. Rossignol, G. L. Dunbar

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)579-588
Number of pages10
JournalRestorative Neurology and Neuroscience
Volume33
Issue number4
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Endothelin-1
Mesenchymal Stromal Cells
Bone Marrow
Stroke
Injections
Aptitude
Memory Disorders
Middle Cerebral Artery
Cause of Death
Animal Models
Transplants
Cognitive Dysfunction

Keywords

  • cognitive dysfunction
  • Endothelin-1
  • mesenchymal stem cells
  • operant conditioning
  • stroke

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke. / Lowrance, S. A.; Fink, Kyle; Crane, A.; Matyas, J.; Dey, N. D.; Matchynski, J. J.; Thibo, T.; Reinke, T.; Kippe, J.; Hoffman, C.; Sandstrom, M.; Rossignol, J.; Dunbar, G. L.

In: Restorative Neurology and Neuroscience, Vol. 33, No. 4, 01.01.2015, p. 579-588.

Research output: Contribution to journalArticle

Lowrance, SA, Fink, K, Crane, A, Matyas, J, Dey, ND, Matchynski, JJ, Thibo, T, Reinke, T, Kippe, J, Hoffman, C, Sandstrom, M, Rossignol, J & Dunbar, GL 2015, 'Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke', Restorative Neurology and Neuroscience, vol. 33, no. 4, pp. 579-588. https://doi.org/10.3233/RNN-130329
Lowrance, S. A. ; Fink, Kyle ; Crane, A. ; Matyas, J. ; Dey, N. D. ; Matchynski, J. J. ; Thibo, T. ; Reinke, T. ; Kippe, J. ; Hoffman, C. ; Sandstrom, M. ; Rossignol, J. ; Dunbar, G. L. / Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke. In: Restorative Neurology and Neuroscience. 2015 ; Vol. 33, No. 4. pp. 579-588.
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AU - Dey, N. D.

AU - Matchynski, J. J.

AU - Thibo, T.

AU - Reinke, T.

AU - Kippe, J.

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