Abstract 191: Neurorestorative Therapy For Stroke In Type 2 Diabetic Rats Using Bone Marrow Stromal Cells
Objective: Treatment of stroke may differ between the diabetic (DM) and non-DM stroke populations. Cell therapy with bone-marrow-stromal cells (BMSC) initiated at 24h after stroke improves functional recovery in non-DM rats, but not in type one DM rats. However, the effect of BMSC treatment of stroke in type two DM (T2DM) is unknown and is the subject of this investigation.
Methods: T2DM was induced with high fat diet and low dose of streptozotocin. T2DM rats were subjected to 2h of middle cerebral artery occlusion (MCAo), then treated with either BMSC (5X106) or vehicle (n=8/group) initiated at 3 days after MCAo and monitored for 28 days. A battery functional tests, and vascular and white matter changes and protein expression were measured in the ischemic brain.
Results: BMSC treatment significantly improved functional outcome at 14 and 21 days after MCAo in T2DM rats. However, the functional benefit was lost at 28 days after MCAo. BMSC significantly increased vascular and white matter remodeling identified by an increase of vascular density (vWF: 403±35/mm2 vs 303±17/mm2), cerebral arteriole number (aSMA 65.0±6.9/mm2 vs 38.6±4.4/mm2), Bielschowsky silver (axon marker, 26±2.4% vs 18±1.8%) and Lucifer fast blue (myelin marker, 39±3.1% vs 25±3.5%) expression in the ischemic boundary zone (IBZ). To test the mechanisms underlying the BMSC induced neurorestorative effects, decreased RAGE and Angiogenin expression were observed in the IBZ (RAGE: 3.1±0.4% vs 13.2±3%; Angiogenin: 9.5±2.2% vs 27.7±5.2%) of BMSC treated rats. However, BMSC treatment significantly increased internal carotid wall thickness (23.4±1.5μm vs 17.9±0.6μm), artery intimae thickness (11.1±0.6μm vs 7.6±0.5μm), and cerebral artery wall thickness (10.5±0.8μm vs 6.4±0.2μm); and significantly decreased cerebral artery diameter (26.5±1.7μm vs 36.3±2.8μm) compared to vehicle control.
Conclusion: BMSC therapy in T2DM-MCAo significantly improved early functional outcome, but did not improve long term functional outcome. BMSC promote vascular and white matter remodeling, but increase cerebral artery neointimal hyperplasia. The increased cerebral artery neointimal hyperplasia may contribute to the failed improvement long term functional outcome after stroke in T2DM rats.
- © 2012 by American Heart Association, Inc.