Blood-brain barrier targeting of BDNF improves motor function in rats with middle cerebral artery occlusion

intravenous brain-derived neurotrophic factor (BDNF) causes a 65-70% reduction in stroke volume in rats with the middle cerebral artery occlusion (MCAO), provided the BDNF is conjugated to a blood-brain barrier (BBB) molecular Trojan horse. The latter may be a peptidomimetic monoclonal antibody (MAb) to the transferrin receptor. The present studies determine whether the effects on stroke volume correlate with an improvement in neurobehavior using the rotarod test. The rotarod latency was > 200 s at 16 RPM in all rats pre-MCAC. The latency was 30 +/- 7 s and 103 +/- 9 s at 24 h post-MCAO in the animals treated with BDNF alone and the BDNF-MAb conjugate, respectively. These studies show that when BDNF is formulated to enable transport across the BBB, the intravenous administration of the neurotrophin results in a reduction in stroke volume that is associated with a parallel improvement in functional outcome. (c) 2006 Elsevier B.V. All rights reserved.