Dietary supplementation exerts neuroprotective effects in ischemic stroke model.
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.
Yasuhara
Takao
T
Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912, USA. cborlongan@mail.mcg.edu
Hara
Koichi
K
Maki
Mina
M
Masuda
Tadashi
T
Sanberg
Cyndy D
CD
Sanberg
Paul R
PR
Bickford
Paula C
PC
Borlongan
Cesar V
CV
D000818:Animals; D029798:Blueberry Plants / Q000737:chemistry; D002545:Brain Ischemia / Q000473:pathology*; D002336:Carnosine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009422:Nervous System Diseases / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology*; D013662:Tea / Q000737:chemistry
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D010936:Plant Extracts; D013662:Tea; D002762:Cholecalciferol; D002336:Carnosine