维持小胶质细胞的修复功能有助于中风的恢复
维持小胶质细胞的修复功能有助于中风的恢复
作者： 小柯机器人 发布时间：2026/5/14 15:11:16
本期文章：《自然》：Online/在线发表
东京科学研究所Takashi Shichita小组近日取得一项新成果。经过不懈努力，他们揭示了维持小胶质细胞的修复功能有助于中风的恢复。2026年5月13日出版的《自然》发表了这项成果。
通过细胞命运分析，研究组发现，即使在中风后失去了有益的功能，修复性小胶质细胞仍然存在于大脑中。在这些细胞中，ZFP384被认为是一种关键的转录调节因子，可以减少与恢复阶段相关的基因的表达，使它们变成功能失调的小胶质细胞，失去其修复功能。在机制上，ZFP384减少了YY1介导的染色质相互作用，这是诱导这些基因在小胶质细胞中表达所必需的。以ZFP384为靶点的反义寡核苷酸可以维持小胶质细胞广泛的神经修复作用，并增强脑卒中后的恢复，即使在缺血性脑卒中的慢性阶段也是如此。因此，预防修复性免疫（免疫细胞有益的恢复功能）丧失的治疗方法可以延长大脑的功能恢复。
据悉，脑损伤后的神经系统症状可能是终身有害的后遗症，因为大多数自发恢复反应在损伤后几个月内消失。小胶质细胞在这个过程中起着至关重要的作用；然而，减少大脑自发功能恢复的细胞和分子机制仍不清楚。
附：英文原文
Title: Sustaining microglial reparative function enhances stroke recovery
Author: Tsuyama, Jun, Sakai, Seiichiro, Kurabayashi, Kumiko, Nakamura, Ayaka, Tanaka, Eri, Hara, Yuichiro, Kawakami, Ito, Tsuda, Makoto, Masuda, Takahiro, Prinz, Marco, Kawaji, Hideya, Shichita, Takashi
Issue&Volume: 2026-05-13
Abstract: Neurological symptoms after brain injury can remain as lifelong detrimental sequelae because most of the spontaneous recovery response disappears within a few months after the injury1,2. Microglia have an essential role in this process; however, the cellular and molecular mechanisms that diminish spontaneous functional recovery in the brain remain unclear. Here using cellular fate analysis, we show that reparative microglia persist in the brain after a stroke even after losing their beneficial functions. In these cells, ZFP384 is identified as a pivotal transcriptional regulator that diminishes the expression of genes associated with the recovery phase, turning them into dysfunctional microglia that lose their reparative functions. Mechanistically, ZFP384 diminishes the YY1-mediated chromatin interaction necessary to induce the expression of these genes in microglia. The use of antisense oligonucleotides that target Zfp384 can sustain the broad range of neural repair effects of microglia and enhance recovery after stroke, even in the chronic phase of ischaemic stroke. Thus, therapeutics that prevent the loss of reparative immunity—the beneficial restorative functions of immune cells—can prolong functional recovery in the brain.
DOI: 10.1038/s41586-026-10480-0
Source: https://www.nature.com/articles/s41586-026-10480-0