title: Endogenous tissue plasminogen activator mediates bone marrow stromal cell-induced neurite remodeling after stroke in mice.
abstract: OBJECTIVE
  Bone marrow stromal cells (BMSC) decrease neurological deficits in rodents after stroke and concomitantly induce extensive neurite remodeling in the brain, which highly correlates with the improvement of neurological function. We investigated the effects of endogenous tissue plasminogen activator (tPA) on neurite remodeling after BMSC treatment.
  
  
  METHODS
  Adult C57BL/6 wild-type (WT) mice and tPA knockout (tPA(-/-)) mice were subjected to middle cerebral artery occlusion, followed by an injection of 1×10(6) BMSC (n=18) or phosphate-buffered saline (n=18) into the tail vein 24 hours later. Behavioral tests were performed at 3, 7, and 14 days after middle cerebral artery occlusion. Animals were euthanized at 14 days after stroke.
  
  
  RESULTS
  The effects of BMSC on functional recovery depended on presence or absence of tPA, even after adjusting for imbalanced stroke severity. BMSC significantly improve functional recovery in WT mice compared to WT controls but show no beneficial effect in the tPA(-/-) mice compared to tPA(-/-) controls. Axonal density and synaptophysin-positive areas along the ischemic boundary zone of the cortex and striatum in WT mice are significantly higher than in the tPA(-/-) mice. BMSC treatment significantly increases tPA protein level and activity only in WT mice.
  
  
  CONCLUSIONS
  Our results suggest that endogenous tPA promotes BMSC-induced neurite outgrowth and may contribute to functional recovery after stroke.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Li Hong
authors.initials: LH
authors.lastname: Shen
authors.forename: Hongqi
authors.initials: H
authors.lastname: Xin
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Cui
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000473:pathology / Q000601:surgery*; D017154:Stromal Cells / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000502:physiology*
chemical_list: D010959:Tissue Plasminogen Activator