Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke

被引：162

作者：

Cook, Douglas J. ^{[1
]}

Nguyen, Cynthia ^{[2
]}

Chun, Hyun N. ^{[2
]}

Llorente, Irene L. ^{[2
]}

Chiu, Abraham S. ^{[2
]}

Machnicki, Michal ^{[2
]}

Zarembinski, Thomas I. ^{[3
]}

Carmichael, S. Thomas ^{[2
]}

机构：

[1] Kingston Gen Hosp, Dept Surg, Div Neurosurg, Kingston, ON, Canada

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[3] BioTime Inc, Alameda, CA USA

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2017年 / 37卷 / 03期

关键词：

Axonal sprouting; bioengineering; hyaluronan; neurogenesis; neural repair; EPIDERMAL-GROWTH-FACTOR; MOTOR RECOVERY; BDNF; NEUROGENESIS; STIMULATION; CELLS; REGENERATION; POLYMORPHISM; ACTIVATION; TRAFERMIN;

D O I：

10.1177/0271678X16649964

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel+BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate (Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel+BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

引用

页码：1030 / 1045

页数：16

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