BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: 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: Petti T Pang; Henry K Teng; Eugene Zaitsev; Newton T Woo; Kazuko Sakata; Shushuang Zhen; Kenneth K Teng; Wing-Ho Yung; Barbara L Hempstead; Bai Lu Journal: Science Date: 2004-10-15 Impact factor: 47.728
Authors: Diego Centonze; Maddalena Napolitano; Emilia Saulle; Paolo Gubellini; Barbara Picconi; Alessandro Martorana; Antonio Pisani; Alberto Gulino; Giorgio Bernardi; Paolo Calabresi Journal: Eur J Neurosci Date: 2002-08 Impact factor: 3.386
Authors: Zhongwu Liu; Yi Li; Li Zhang; Hongqi Xin; Yisheng Cui; Leah R Hanson; William H Frey; Michael Chopp Journal: Neurobiol Dis Date: 2011-11-15 Impact factor: 5.996
Authors: Hongqi Xin; Yi Li; Ben Buller; Mark Katakowski; Yi Zhang; Xinli Wang; Xia Shang; Zheng Gang Zhang; Michael Chopp Journal: Stem Cells Date: 2012-07 Impact factor: 6.277
Authors: Hongqi Xin; Yi Li; Li Hong Shen; Xianshuang Liu; Ann Hozeska-Solgot; Rui Lan Zhang; Zheng Gang Zhang; Michael Chopp Journal: J Cereb Blood Flow Metab Date: 2011-08-10 Impact factor: 6.200
Authors: Hongqi Xin; Michael Chopp; Li Hong Shen; Rui Lan Zhang; Li Zhang; Zheng Gang Zhang; Yi Li Journal: Neurosci Lett Date: 2013-03-07 Impact factor: 3.046