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Dietary supplementation exerts neuroprotective effects in ischemic stroke model.Yasuhara T, Hara K, Maki M, Masuda T, Sanberg CD, Sanberg PR, Bickford PC, Borlongan CV Department of Neurology, Medical College of Georgia, Augusta, Georgia. ABSTRACT This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine (n = 8), or vehicle (n = 7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (p < 0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential. Published 18 February 2008 in Rejuvenation Res, 11(1): 201-14.
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