Stroke and related vascular events can cause widespread damage to the central nervous system (CNS) and result in significant motor and cognitive impairments. It has been suggested that trophic factor treatment may reduce the extent of damage and restore damaged neurons following the injury. We have previously tested the effects of bone morphogenetic protein-7 (BMP-7), a member of the transforming growth factor-B superfamily of growth factors, in focal brain ischemic injury. We found BMP-7 to have profound neuroprotective effects after intraventricular administration. We have now proceeded to test its distribution in the ischemic brain, in order to determine how rapidly BMP-7 may diffuse through brain parenchyma. We also determined whether it has effects on expression of intermediate filaments in neurons short-term after the injury as a partial basis for its restorative activity. Adult male Sprague-Dawley rats were subjected to a 60-minute occlusion of the right middle cerebral artery, and 24 hours thereafter, injections of BMP-7 or vehicle into the lateral ventricle on the ipsilateral side, at a dose of 25 ul (1 ug/ul), were performed. The animals were sacrificed 1, 3, 6, and 24 hours following the BMP-7 administration. In terms of localization in the brain parenchyma, we found that BMP-7 was mostly present in the ependyma 1 hour following injection, while it extended to a few adjacent neurons at 3 hours post-injection. However, the 6- and 24-hour groups both had significant BMP-7-immunoreactive labeling in neurons, primarily in the striatum and thalamus. Neurofilament expression appeared to be fairly weak on the injected side in animals that had received the vehicle injection, whereas a significant upregulation in neurofilament staining was observed at 6- and 24 hours post-injection of BMP-7. Significant neurite outgrowth, with obvious growth cones, was observed at 24 hours, particularly in the ventral striatum and accumbens. These results suggest that BMP-7 injection may aid in the expression of intermediate neuronal filaments following an ischemic injury, and furthermore that the injected factor can become incorporated into neurons located several millimeters from the lateral ventricle.
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