Nano-particle delivery of brain derived neurotrophic factor after focal cerebral ischemia reduces tissue injury and enhances behavioral recovery.
Nano-particle delivery of brain derived neurotrophic factor after focal cerebral ischemia reduces tissue injury and enhances behavioral recovery.
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DOI：
10.1016/j.pbb.2016.09.003
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发表时间：
2016-11
影响因子：
3.6
通讯作者：
Verma, Rajkumar
中科院分区：
文献类型：
--
作者：
Harris, Nia M.;Ritzel, Rodney;Mancini, Nikolas;Jiang, Yuhang;Yi, Xiang;Manickam, Devika S.;Banks, William A.;Kabanov, Alexander V.;McCullough, Louise D.;Verma, Rajkumar
脑源性神经营养因子（BDNF）水平低与中风后神经功能恢复延迟、抑郁和认知障碍有关。补充BDNF可以逆转这些作用。不幸的是，由于其差的血脑屏障渗透性和短的血清半衰期，以其天然形式全身施用的BDNF具有最小的治疗价值。在这项研究中，一种新的纳米颗粒聚离子复合物制剂的BDNF（纳米BDNF）的小鼠实验性缺血性中风后。雄性C57 BL/6 J（8-10周）小鼠在经历60分钟的可逆性大脑中动脉闭塞（MCAo）后被随机分配接受纳米BDNF、天然BDNF或盐水治疗。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）接受第一次给药;所有队列在中风发作后24小时接受第二次给药。卒中后15天通过行为学、组织学和分子分析评估卒中后结局。早期和中期纳米BDNF治疗导致脑组织损失显着减少。延迟治疗可改善记忆/认知，减少卒中后抑郁表型，维持髓鞘碱性蛋白和脑BDNF水平，但对组织萎缩没有影响。结果表明，给予BDNF的新型纳米颗粒制剂导致中风后的神经保护和神经恢复作用。
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 (8–10 weeks) mice were randomly assigned to receive nano-BDNF, native-BDNF, or saline treatment after being subjected to 60 minutes of reversible middle cerebral artery occlusion (MCAo). Mice received the first dose at 3 (early treatment), 6 (intermediate treatment), or 12 hours (delayed treatment) following stroke onset; a second dose was given in all cohorts at 24 hours after stroke onset. Post-stroke outcome was evaluated by behavioral, histological, and molecular analysis for 15 days 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.
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DOI：
10.2147/dddt.s56071
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
通讯作者：
Kleinschnitz C
影响因子：
3.7
作者：
Béjot Y;Mossiat C;Giroud M;Prigent-Tessier A;Marie C
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Marie C
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影响因子：
8.8
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DOI：
10.1186/s13231-014-0012-0
发表时间：
2015
期刊：
Experimental & translational stroke medicine
影响因子：
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作者：
Hong SH;Khoutorova L;Bazan NG;Belayev L
通讯作者：
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影响因子：
7.6
作者：
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