title: Spinal cord blood flow and blood vessel permeability measured by dynamic computed tomography imaging in rats after localized delivery of fibroblast growth factor.
abstract: Following spinal cord injury, profound vascular changes lead to ischemia and hypoxia of spinal cord tissue. Since fibroblast growth factor 2 (FGF2) has angiogenic effects, its delivery to the injured spinal cord may attenuate the tissue damage associated with ischemia. To limit systemic mitogenic effects, FGF2 was delivered to the spinal cord via a gel of hyaluronan and methylcellulose (HAMC) injected into the intrathecal space, and compared to controls receiving HAMC alone and artificial cerebrospinal fluid (aCSF) alone. Dynamic perfusion computed tomography (CT) was employed for the first time in small animals to serially measure blood flow and permeability in the injured and uninjured spinal cord. Spinal cord blood flow (SCBF) and permeability-surface area (PS) measurements were obtained near the injury epicenter, and at two regions rostral to the epicenter in animals that received a 26-g clip compression injury. As predicted, SCBF measurements decreased and PS increased after injury. FGF2 delivered via HAMC after injury restored SCBF towards pre-injury values in all regions, and increased blood flow rates at 7 days post-injury compared to pre-injury measurements. PS was stabilized at regions rostral to the epicenter of injury when FGF2 was delivered with HAMC, with significantly lower values than aCSF controls at 7 days in the region farthest from the epicenter. Laminin staining for blood vessels showed a qualitative increase in vessel density after 7 days when FGF2 was locally delivered. Additionally, permeability stains showed that FGF2 moderately decreased permeability at 7 days post-injury. These data demonstrate that localized delivery of FGF2 improves spinal cord hemodynamics following injury, and that perfusion CT is an important technique to serially measure these parameters in small animal models of spinal cord injury.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Kang
authors.forename: Richard
authors.initials: R
authors.lastname: Clarkson
authors.forename: Charles H
authors.initials: CH
authors.lastname: Tator
authors.forename: Ivan W T
authors.initials: IW
authors.lastname: Yeung
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D002199:Capillary Permeability / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D005079:Excipients; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D005782:Gels; D006820:Hyaluronic Acid; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008747:Methylcellulose; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D005079:Excipients; D005782:Gels; D005346:Fibroblast Growth Factors; D006820:Hyaluronic Acid; D008747:Methylcellulose