Harris Nia M, Ritzel Rodney, Mancini Nickolas S, Jiang Yuhang, Yi Xiang, Manickam Devika S, Banks William A, Kabanov Alexander V, McCullough Louise D, Verma Rajkumar
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06032, USA.
Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill,, Chapel Hill, NC 27599-7362, USA.
Pharmacol Biochem Behav. 2016 Nov-Dec;150-151:48-56. doi: 10.1016/j.pbb.2016.09.003. Epub 2016 Sep 13.
Low levels of brain-derived neurotrophic factor (BDNF) are linked to delayed neurological recovery, depression, and cognitive impairment following stroke. Supplementation with BDNF reverses these effects. Unfortunately, systemically administered BDNF in its native form has minimal therapeutic value due to its poor blood brain barrier permeability and short serum half-life. In this study, a novel nano-particle polyion complex formulation of BDNF (nano-BDNF) was administered to mice after experimental ischemic stroke.
Male C57BL/6J (8-10weeks) mice were randomly assigned to receive nano-BDNF, native-BDNF, or saline treatment after being subjected to 60min of reversible middle cerebral artery occlusion (MCAo). Mice received the first dose at 3 (early treatment), 6 (intermediate treatment), or 12h (delayed treatment) following stroke onset; a second dose was given in all cohorts at 24h after stroke onset. Post-stroke outcome was evaluated by behavioral, histological, and molecular analysis for 15days after stroke.
Early and intermediate nano-BDNF treatment led to a significant reduction in cerebral tissue loss. Delayed treatment led to improved memory/cognition, reduced post-stroke depressive phenotypes, and maintained myelin basic protein and brain BDNF levels, but had no effect on tissue atrophy.
The results indicate that administration of a novel nano-particle formulation of BDNF leads to both neuroprotective and neuro-restorative effects after stroke.
脑源性神经营养因子（BDNF）水平低下与中风后神经功能恢复延迟、抑郁及认知障碍有关。补充BDNF可逆转这些影响。遗憾的是，天然形式的BDNF经全身给药后，因其血脑屏障通透性差和血清半衰期短，治疗价值极小。在本研究中，一种新型的BDNF纳米颗粒聚离子复合物制剂（纳米BDNF）在实验性缺血性中风后给予小鼠。
雄性C57BL/6J（8 - 10周）小鼠在经历60分钟可逆性大脑中动脉闭塞（MCAo）后，随机分配接受纳米BDNF、天然BDNF或生理盐水治疗。小鼠在中风发作后3小时（早期治疗）、6小时（中期治疗）或12小时（延迟治疗）接受第一剂；所有组在中风发作后24小时给予第二剂。中风后15天通过行为、组织学和分子分析评估中风后结局。
早期和中期纳米BDNF治疗导致脑组织损失显著减少。延迟治疗改善了记忆/认知，减少了中风后抑郁表型，并维持了髓鞘碱性蛋白和脑BDNF水平，但对组织萎缩没有影响。
结果表明，给予新型BDNF纳米颗粒制剂可在中风后产生神经保护和神经修复作用。
