Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion.

Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion.
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DOI:
10.1002/adma.201606471
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发表时间:
2017-08
期刊:
Advanced materials (Deerfield Beach, Fla.)
影响因子:
--
通讯作者:
Segura T
Segura T
中科院分区:
其他
文献类型:
--
作者:
Nih LR;Sideris E;Carmichael ST;Segura T

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随着中风死亡人数的减少,更多的人被迫生活在中风造成的严重残疾中。迄今为止,除了休息和物理治疗外,在中风发作后的前4.5小时后没有治疗方法。中风后,大量星形胶质细胞和小胶质细胞释放促炎细胞因子,导致严重的炎症和胶质瘢痕形成,影响脑组织的自我修复能力。病理条件如中风触发神经祖细胞(NPC)增殖和向受损部位迁移。然而,这些祖细胞通常被发现远离腔或梗死周围组织。中风后组织重塑导致腔室分隔,可以直接接受治疗材料注射。在这里,我们表明,注射到中风腔的多孔透明质酸水凝胶显着减少中风后的炎症反应,同时增加梗死周围血管化相比,无孔水凝胶控制和中风只有控制。此外,我们表明,我们的材料的注射影响NPC的增殖和迁移在脑室下区龛和结果,第一次,在NPC迁移到中风部位。颗粒水凝胶可以注射到中风腔中并原位退火以在微创手术中形成微孔支架。我们表明,这种颗粒水凝胶支架减少神经胶质增生,同时增加梗死周围血管和促进神经祖细胞浸润到水凝胶。
With the number of deaths due to stroke decreasing, more individuals are forced to live with crippling disability resulting from the stroke. To date, no therapeutics exist after the first 4.5 hours after the stroke onset, aside from rest and physical therapy. Following stroke, a large influx of astrocytes and microglia releasing pro-inflammatory cytokines leads to dramatic inflammation and glial scar formation, affecting brain tissue's ability to repair itself. Pathological conditions such as a stroke trigger neural progenitor cells (NPCs) proliferation and migration toward the damaged site. However, these progenitors are often found far from the cavity or the peri-infarct tissue. Post stroke tissue remodeling results in a compartmentalized cavity that can directly accept a therapeutic material injection. Here, we show that the injection of a porous hyaluronic acid hydrogel into the stroke cavity significantly reduces the inflammatory response following stroke while increasing peri-infarct vascularization compared to non-porous hydrogel controls and stroke only controls. In addition, we show that the injection of our material impacts NPCs proliferation and migration at the subventricular zone niche and results, for the first time, in NPC migration into the stroke site. Particle hydrogels can be injected into the stroke cavity and anneal in situ to form a microporous scaffold in a minimally invasive procedure. We show that this particle hydrogel scaffold decreases gliosis, while increasing the peri-infarct vasculature and promoting neural progenitor cell infiltration into the hydrogel.
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