title: Axonal sprouting into the denervated spinal cord and synaptic and postsynaptic protein expression in the spinal cord after transplantation of bone marrow stromal cell in stroke rats.
abstract: We investigated whether compensatory reinnervation in the corticospinal tract (CST) and the corticorubral tract (CRT) is enhanced by the administration of bone marrow stromal cells (BMSCs) after experimental stroke. Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Phosphate-buffered saline (PBS, control, n=7) or 3x10(6) BMSCs in PBS (n=8) were injected into a tail vein at 1 day postischemia. The CST of the left sensorimotor cortices was labeled with DiI 2 days prior to MCAo. Functional recovery was measured. Rats were sacrificed at 28 days after MCAo. The brain and spinal cord were removed and processed for vibratome sections for laser-scanning confocal analysis and paraffin sections for immunohistochemistry. Normal rats (n=4) exhibited a predominantly unilateral pattern of innervation of CST and CRT axons. After stroke, bilateral innervation occurred through axonal sprouting of the uninjured CRT and CST. Administration of BMSCs significantly increased the axonal restructuring on the de-afferented red nucleus and the denervated spinal motoneurons (p<0.05). BMSC treatment also significantly increased synaptic proteins in the denervated motoneurons. These results were highly correlated with improved functional outcome after stroke (r>0.81, p<0.01). We conclude that the transplantation of BMSCs enhances axonal sprouting and rewiring into the denervated spinal cord which may facilitate functional recovery after focal cerebral ischemia.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Runjiang
authors.initials: R
authors.lastname: Qu
authors.forename: Lihong
authors.initials: L
authors.lastname: Shen
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Xueguo
authors.initials: X
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Smita
authors.initials: S
authors.lastname: Savant-Bhonsale
authors.forename: Jade
authors.initials: J
authors.lastname: Borneman
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D003714:Denervation; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D018613:Microscopy, Confocal; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013116:Spinal Cord / Q000473:pathology* / Q000502:physiology; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D017154:Stromal Cells / Q000637:transplantation*