Abstract WP111: The Impact Of Statins On The Blood Brain Barrier Might Adversely Affect Autologous Bone Marrow Cell Therapy In Acute Stroke
Background: Autologous bone marrow derived mononuclear cells (MNCs) enhance stroke recovery in animals and are being tested in stroke clinical trials. Some patients at the time of stroke are on statins, which reduce blood-brain barrier permeability. Since MNCs may need to enter the brain to enhance brain repair, statins might reduce the efficacy of MNCs. We studied the impact of statin exposure on MNC delivery into the brain.
Methods: In this double blind placebo controlled experiment, 30 Long Evans rats were randomized into 4 groups (fig). Stroke was induced by MCA suture occlusion for 90 min. Atorvastatin (or vehicle) was given PO daily for 5 days before stroke. Animals that received MNCs underwent a bone marrow harvest at 22 hrs after stroke followed by isolation, labeling with Q-tracker, and MNC re-infusion by intra-carotid artery delivery. BBB permeability was assessed by Evans Blue.
Results: Pre-treatment with atorvastatin and post-treatment with MNCs led to a significant reduction in BBB breakdown. (p = 0.003). Neither atorvastatin nor MNCs alone had a significant effect on the BBB. Pre-treatment with atorvastatin significantly reduced the number of MNCs in the brain (p = .02)
Conclusions: Exposure to atorvastatin before stroke reduces the number of MNCs entering the brain when the cells are administered at 24 hrs after stroke. Atorvastatin in combination with MNCs led to substantial reduction in BBB permeability, suggesting that atorvastatin and MNCs may have a synergistic effect on the BBB which could consequently prevent CNS entry of MNCs. These results have important translational implications for the design of clinical trials testing bone marrow cell therapies in patients with acute stroke. Statins might potentially reduce the number of cells entering the brain which could reduce the potential benefits of cell therapies that need to enter the brain to enhance recovery. We are studying if atorvastatin impairs recovery in rats treated with MNCs.
- © 2012 by American Heart Association, Inc.