Abstract
AimsOur previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.MethodsT1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×106); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×106) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days.ResultsCombination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals.ConclusionsCombination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.
Highlights
Diabetes mellitus (DM) is a leading health concern [1] that substantially elevates the risk of occurrence and recurrence of ischemic stroke [2,3,4]
We did not find that combination treatment significantly improved functional outcome after stroke in T1DM control rats when compared to T1DM control or bonemarrow-stromal cells (BMSC) monotherapy groups
Combination BMSC and Niaspan treatment of stroke in T1DM initiated at 24h after middle cerebral artery occlusion (MCAo) did not decrease lesion volume (Figure 1C)
Summary
Diabetes mellitus (DM) is a leading health concern [1] that substantially elevates the risk of occurrence and recurrence of ischemic stroke [2,3,4]. Post stroke outcomes and fatality rates are significantly worse in the diabetic population [5,6]. Compared to the non-diabetic cases, DM patients face greater residual neurological and functional disability [3]. Previous studies have found that cell therapy with bonemarrow-stromal cells (BMSC) improves functional recovery after stroke in non-diabetic rats [8,9]. BMSC have the ability to pass the blood brain barrier (BBB) and selectively target damaged brain, secrete growth factors [8,9,10], increase angiogenesis and synaptogenesis [11], as well as improve functional recovery after stroke and traumatic brain injury [9,12,13]
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