MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury.
Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.
Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Lian
L
Li
Michael
M
Chopp
Guang Liang
GL
Ding
Chang Sheng
CS
Qu
Qing Jiang
QJ
Li
Mei
M
Lu
Shiyang
S
Wang
Siamak P
SP
Nejad-Davarani
Asim
A
Mahmood
Quan
Q
Jiang
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000503:physiopathology* / Q000628:therapy*; D001931:Brain Mapping; D002552:Cerebral Ventricles / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003627:Data Interpretation, Statistical; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation*; D016896:Treatment Outcome