脑出血
医学
炎症
药理学
血肿
小胶质细胞
神经炎症
全身给药
免疫学
麻醉
生物
外科
体内
生物技术
蛛网膜下腔出血
作者
Kuan-Yin Tseng,Vassilis Stratoulias,Wei-Fen Hu,Jui‐Sheng Wu,Vicki Wang,Yuan-Hao Chen,Anna Seelbach,Henri J. Huttunen,Natalia Kulesskaya,Cheng‐Yoong Pang,Jian‐Liang Chou,Maria Lindahl,Märt Saarma,Li‐Chuan Huang,Mikko Airavaara,Hock‐Kean Liew
标识
DOI:10.1038/s41419-022-05520-2
摘要
Abstract During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to release hemoglobin and heme, which act as neurotoxins and induce inflammation and secondary brain injury, resulting in severe neurological deficits. Accelerating hematoma resorption and mitigating hematoma-induced brain edema by modulating immune cells has potential as a novel therapeutic strategy for functional recovery after ICH. Here, we show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain’s myeloid cells for the treatment of ICH.
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