title: Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke.
abstract: OBJECTIVE
  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.
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Lowrance
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Fink
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Crane
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Matyas
authors.affiliation: Field Neurosciences Institute, Saginaw, MI, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Dey
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Matchynski
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Thibo
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Reinke
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kippe
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hoffman
authors.affiliation: Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sandstrom
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.|Central Michigan University College of Medicine, Mount Pleasant, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rossignol
authors.affiliation: Field Neurosciences Institute Laboratory for Restorative Neurology, Mount Pleasant, MI, USA.|Central Michigan University Program in Neuroscience, Mount Pleasant, MI, USA.|Field Neurosciences Institute, Saginaw, MI, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000473:pathology; D002908:Chronic Disease; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D019332:Endothelin-1; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D011581:Psychological Tests; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D019332:Endothelin-1
keywords: Endothelin-1; cognitive dysfunction; mesenchymal stem cells; operant conditioning; stroke