The Effect of the Dendritic Growth Factor BMP-7 on Local Cerebral Glucose Utilization and Blood Flow in Reversible Middle Cerebral Artery Occlusion in Rats
Bone morphogenetic protein-7 (BMP-7) (=osteogenic protein-1, OP-1) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine coated intraluminal suture (1). Rectal and cranial (left temporalis muscle) temperatures were regulated at 37–37.5oC. BMP-7 or vehicle (volume, 25μl) was administered intracisternally in blinded fashion at 24h after MCAo. Neurological status was evaluated during occlusion (60 min) and daily for 2 days after MCAo; a grading scale of 0–12 was employed (1). LCMRglu was measured autoradiographically with 14C-2 deoxyglucose (2-DG) and LCBF with 14C-iodoantipyrine 48 h after MCAo. Four animals groups were studied: LCMRglu series (BMP-7, n=7; vehicle, n=8); LCBF series (BMP-7, n=6; vehicle, n=8). Average three-dimensional image data sets were constructed for each group and were compared by pixel-based statistical methods (2). Rectal and cranial temperatures, MABP, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the neurological score compared to vehicle at 48 after MCAo (7.3 ± 0.4 vs. 9.0 ± 0.2, respectively; p<0.0003). Compared to vehicle-rats, BMP-7 significantly increased LCMRglu in ipsilateral basal ganglia, improved LCBF in ipsilateral subthalamus, and decreased LCBF and LCMRglu in contralateral cortical regions. The improved glucose metabolism in ipsilateral basal ganglia of BMP-7 rats is compatible with its salutary influence on neurological recovery. Supported by Creative BioMolecules, Inc., Hopkinton, MA, and by NIH Grant NS 05820. (1)Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD: Stroke 27:1616–1623,1996. (2)Zhao W, Belayev L, Ginsberg MD: J Cereb Blood Flow Metab 17:1281–1290,1997.