Abstract 3053: Combination Niaspan With Bone Marrow Stromal Cell Treatment Of Stroke In Diabetic Rats
Background and Purpose: Our previous studies have found that cell therapy with bone-marrow-stromal cells (BMSCs) improves functional recovery after stroke in non-diabetic, but not in diabetic rats. BMSC treatment of stroke in type one diabetic (T1DM) rats increases brain hemorrhage and arteriosclerosis. Niaspan (a prolonged release formulation of niacin) treatment of stroke increases vascular stabilization and decreases arteriosclerosis in wild type (WT) rats. This study investigated the effect of combination therapy of BMSCs with Niaspan on stroke outcome and arteriosclerosis in T1DM rats.
Methods: T1DM was induced in adult male Wistar rats by injecting streptozotocin. Non-diabetic and T1DM-rats were subjected to 2hours of middle cerebral artery occlusion (MCAo). The rats were treated with: 1) PBS as control; 2) BMSCs BMSCs (3X106) alone; 3) Niaspan (40mg/kg) alone daily for 14 days; 4) BMSCs (3X106)+Niaspan (40mg/kg, daily for 14 days) combination starting at 24 hours after MCAo and rats monitored for 14 days.
Results: Functional benefit was not detected in T1DM-MCAo treated with BMSCs rats compared to T1DM-MCAo controls. BMSC treatment in T1DM-MCAo-rats had increased mortality, blood-brain barrier (BBB) leakage and brain hemorrhage. Internal carotid artery neointimal formation and cerebral arteriole narrowing/occlusion were also observed in T1DM-MCAo+BMSCs rats compared to T1DM-MCAo controls (p<0.05). We further studied the underlying mechanisms responsible for BMSC-induced BBB leakage and accelerated vascular damage in T1DM-MCAo-rats. We found that the expression of angiogenin (an angiogenic factor) and ED1 (a marker for macrophages) were significantly increased in the T1DM-MCAo+BMSCs rats in the ischemic brain and in the internal carotid artery compared to non-treated T1DM-MCAo rats. However, combination BMSCs with Niaspan significantly improves functional outcome after stroke, decreases Angiogenin, ED1 and MMP9 expression in the ischemic brain as well as decreases brain hemorrhage and cerebral arteriosclerosis compared to T1DM-MCAo control or T1DM+BMSCs alone groups.
Conclusions: Combination therapy using BMSCs with Niaspan improves functional outcome and decreases BBB leakage and cerebral artery neointimal formation and arteriosclerosis. This therapeutic benefit may be attributed to the combination mediated decreased expression of angiogenin and anti-inflammatory effects.
- © 2012 by American Heart Association, Inc.