Increasing numbers of individuals live with stroke related disabilities. Following stroke, highly reactive astrocytes and pro-inflammatory microglia can release cytokines and lead to a cytotoxic environment that causes further brain damage and prevents endogenous repair. Paradoxically, these same cells also activate pro-repair mechanisms that contribute to endogenous repair and brain plasticity. Here, it is shown that the direct injection of a hyaluronic acid-based microporous annealed particle (MAP) hydrogel into the stroke core in mice reduces the percent of highly reactive astrocytes, increases the percent of alternatively activated microglia, decreases cerebral atrophy, and preserves NF200 axonal bundles. Further, MAP hydrogel is shown to promote reparative astrocyte infiltration into the lesion, which directly coincides with axonal penetration into the lesion. This work shows that the injection of a porous scaffold into the stroke core can lead to clinically relevant decrease in cerebral atrophy and modulates astrocytes and microglia toward a pro-repair phenotype.

中文翻译：

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颗粒水凝胶可减少中风后脑萎缩并减弱星形胶质细胞和小胶质细胞/巨噬细胞的反应性

越来越多的人患有中风相关残疾。中风后，高反应性星形胶质细胞和促炎性小胶质细胞可以释放细胞因子并导致细胞毒性环境，导致进一步的脑损伤并阻止内源性修复。矛盾的是，这些相同的细胞也激活促修复机制，有助于内源性修复和大脑可塑性。在这里，研究表明，将基于透明质酸的微孔退火颗粒（MAP）水凝胶直接注射到小鼠中风核心中，可以减少高反应性星形胶质细胞的百分比，增加替代激活的小胶质细胞的百分比，减少脑萎缩，并保留NF200 轴突束。此外，MAP 水凝胶被证明可以促进修复性星形胶质细胞浸润到病变中，这与轴突渗透到病变中直接一致。这项工作表明，将多孔支架注射到中风核心中可以导致临床相关的脑萎缩减少，并将星形胶质细胞和小胶质细胞调节为促修复表型。